Histogram views are shown when there are more than 50 features on a single chromosome. Please click on the histogram to view individual features at that position.

{"CNV":[{"assembly":"GRCh37/hg19","short_description":"1p36 microdeletion syndrome","remap_value":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Monosomy 1p36 is the most common terminal deletion syndrome, estimated at ~1/5,000 births (Shaffer & Lupski 2000). Features include microcephaly and brachycephaly in addition to growth retardation which can be pre- or postnatal in onset. Facial characteristics include deep-set eyes, a flat nasal bridge, asymmetric ears and a pointed chin. Straight eyebrows are another characteristic feature. The main clinical features include developmental delay (100%) with hypotonia (100%), seizures (up to 72%), cardiac defects (40%) including dilated cardiomyopathy (~23%) and cleft lip/palate (20-40%). Mild high frequency sensorineural hearing loss is very common (Heilstedt). Seizures are possibly caused by haploinsufficiency for the \u003ci\u003eKCNAB2\u003c/i\u003e gene and there is no specific seizures type. The distal end of 1p is very gene rich; Gajecka et al (2007)discuss the gene content of the region with respect to phenotype and candidate gene content.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e This varies widely from ~1.5Mb - \u003e10Mb. 40% of all breakpoints occur 3.0-5.0Mb from the telomere. 70% have true terminal deletions. A few (~7%) of 1p36 deletions are interstitial, retaining the 1p subtelomeric region of the 1pTAR. Others have a derivative chromosome 1 in which the 1p telomere is replaced by another chromosome end occurring either \u003ci\u003ede novo\u003c/i\u003e or as a consequence of a balanced parental translocation. Breakpoints are most commonly 1p36.13 - 1p36.33. Only ~2/3rds of \u003ci\u003ede novo\u003c/i\u003e rearrangements are apparently simple terminal truncations at the DNA sequence level. The remaining 1/3rd are complex structures including deletions with interrupted inverted duplications, large duplications and triplications with small terminal deletions, or more than one interstitial deletion on a single chromosome with normal intervening sequence (Gajecka 2007).\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e Of \u003ci\u003ede novo\u003c/i\u003e terminal deletions, the incidence of maternal and paternal deletions is roughly equal. In general, deletions arising on the maternal homologue tend to be smaller than deletions arising on the paternal homologue.\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e - Anne Slavotinek, Assistant Professor of Clinical Pediatrics, University of California, San Francisco, USA\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.1p36.com/\"\u003ewww.1p36.com\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.1p36dsa.org/\"\u003ewww.1p36dsa.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%201/1p36%20deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1191/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1606\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","original_position":null,"id":25,"grade":1,"remapped_from":null,"syndrome_cnv_id":25,"updated":"2014-07-02 09:23:45.946508","end":12840259,"is_draft":0,"start":10001,"syndrome_id":18,"chr":"1","genotype":"Heterozygous","created":"2012-07-31 12:47:28"},{"chr":"1","genotype":"Heterozygous","created":"2012-08-01 11:30:16","syndrome_cnv_id":64,"updated":"2014-07-02 09:23:46.005983","end":145748067,"is_draft":0,"start":145386506,"syndrome_id":64,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia, but with presence of both thumbs. Klopocki et al. propose that TAR syndrome is a complex trait requiring at least two unlinked alleles - one rare (1q21.1 microdeletion) and the other frequent (currently unknown modifier of TAR factor [mTAR]). \u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Klopocki found that 28/30 patients had a microdeletion spanning ~500kb, but one patient had smaller deletions measuring ~200kb, but with a typical TAR phenotype and another had a slightly larger deletion. Thus the deletion common to all TAR patients in Klopocki's study measured ~200kb and contains ~12 genes.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e In Klopocki's study of TAR patients, the deletion occurred \u003ci\u003ede novo\u003c/i\u003e in ~25% of patients, but was inherited from apparently unaffected mothers or fathers in the remainder. The fact that the microdeletion was observed in both mothers and fathers makes genomic imprinting an unlikely explanation.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Prof Dr Stefan Mundlos, Max-Planck-Institut fur Molekulare Genetik, Berlin, Germany\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ivh.se/TAR/\"\u003ewww.ivh.se\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%201/1q21.1%20Microdeletions%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK23758/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=3320\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/5116/tar-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","copy_number":1,"id":64,"original_position":null,"grade":3,"remapped_from":null,"short_description":"1q21.1 susceptibility locus for Thrombocytopenia-Absent Radius (TAR) syndrome","assembly":"GRCh37/hg19","remap_value":null},{"original_position":null,"id":67,"grade":3,"remapped_from":null,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Mefford (2008) identified 9 patients with the recurrent duplication, one of whom also carried a second large chromosome abnormality. Of the remaining eight patients, five (63%) had a history of mild/moderate developmental delay and dysmorphic features (but note that these are the commonest indications for genomic array analysis). In addition four patients (50%) had macrocephaly or relative macrocephaly, and four had autism or autistic behaviours. Two parents carried the same duplication as their affected offspring, but were phenotypically normal and showed normal cognitive development. The finding that some carriers of the 1q21.1 microduplication do not have a phenotype implies that there is incomplete penetrance, or that there are important modifiers acting on this locus. Brunetti-Pierri et al (2008) confirmed the association with head growth, the microduplication associated with increased brain sizew whilst the reciprocal microdeletion is associated with reduction in brain size.\u003c/p\u003e\u003cp\u003eThe phenotypic diversity, incomplete penetrance and lack of distinct syndromic features associated with 1q21 rearrangements make genetic counselling for this rearrangement problematic. The frequency of the 1.35 Mb duplication appears to be enriched in individuals with neurodevelopmental disorders compared with controls. Mefford (2008) found the 1q21.1 duplication in 9/5218 patients and 1/4737 controls (p=0.02). The different prevalence of this rearrangement in patient and control populations suggests that this is a clinically relevant finding that appears to predispose to neurodevelopmental problems and autism. The Autism Genome Project Consortium reported three duplication cases in association with autism (one of these was inherited from a normal father). Note that the frequency of 1q2.1 duplications in this population was only 0.25% and the frequency in the normal population has not yet been well established).\r\u003c/p\u003e\u003cp\u003eThere is a reciprocal 1q21.1 deletion that appears to occur more commonly than the duplication. At the present time the 1q21.1 recurrent microduplication may be best regarded as a susceptibility locus rather than a clinically distinct syndrome.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e The minimal duplication region is ~1.35Mb and includes at least 7 genes(Mefford). \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e The flanking regions contain a significant density of segmental duplications and a large inversion polymorphism spans the recurrent deletion/duplication region. Breakpoints of the most common ~1.35Mb duplication map to BP3 and BP4 suggesting non-allelic homologous recombination as the mechanism generating the duplication and its reciprocal deletion. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Andy Sharp, University of Washington, Department of Genetic Medicine and Development, University of Geneva, Switzerland\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%201/1q21.1%20microduplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=250994\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":3,"variant_class":"Duplication","remap_value":null,"short_description":"1q21.1 recurrent microduplication (possible susceptibility locus for neurodevelopmental disorders)","assembly":"GRCh37/hg19","created":"2012-08-01 11:42:03","genotype":"Heterozygous","chr":"1","start":146533376,"syndrome_id":67,"is_draft":0,"end":147883376,"updated":"2014-07-02 09:23:46.225586","syndrome_cnv_id":67},{"remap_value":null,"short_description":"1q21.1 recurrent microdeletion (susceptibility locus for neurodevelopmental disorders)","assembly":"GRCh37/hg19","remapped_from":null,"id":63,"original_position":null,"grade":3,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e This region is distinct from, but very close to, the 1q21.1 microdeletion which has been reported in patients with TAR syndrome. A reciprocal duplication has been reported. The phenotype associated with microdeletion of 1q21.1 is highly variable, ranging from asymptomatic to severe developmental delay and multiple congenital anomalies. It was originally reported in 3 of a cohort of 505 individuals with congenital heart disease (Christiansen 2004), but was also present in unaffected parents. Mefford (2008) identified 25 persons with the recurrent deletion from a sample of 5218 patients, and showed that the deletion was absent from a series of 4737 controls (p=1.1x10-7). \u003c/p\u003e\u003cp\u003eIn Mefford's series, the majority of patients with a deletion had a history of mild/moderate developmental delay (16/21) and dysmorphic features (17/21) (but note that these are the commonest indications for genomic array analysis). 3 parents were also mildly affected, but 5 probands and 4 parents had normal cognitive development. The finding that some carriers of the 1q21.1 microdeletion do not have a phenotype implies that there is incomplete penetrance, or that there are important modifiers acting on this locus. In addition 14/21 patients (67%) and 2 parents with the deletion had microcephaly or relative microcephaly indicating an influence of this genomic region on brain growth. Brunetti-Pierri et al (2008) confirmed the association with head growth, withe microdeletion associated with reduction in brain size and conversely, the reciprocal duplication associated with increased brain size. Other features noted in multiple cased include congenital heart abnormality (6/21), ligamentous laxity or joint hypermobility (5/21), hypotonia (5/21), seizures (3/21) and cataracts (3/21). Apparently identical deletions of 1q21.1 have also been found to be significantly enriched in patients with non-syndromic schizophrenia, although occurring at a very low frequency (0.26%). Combining data from two studies, a total of 21 of 8109 schizophrenia cases, compared to 9 of 44,380 controls, were found to carry deletions of 1q21.1 (Stefansson et al 2008; International Schizophrenia consortium 2008).\r\u003c/p\u003e\u003cp\u003eThe phenotypic diversity, incomplete penetrance and lack of distinct syndromic features associated with 1q21 rearrangements make genetic counselling for this rearrangement problematic. Nevertheless the different prevalence of this rearrangement in patient and control populations suggests that this is a clinically relevant finding that appears to predispose to neurodevelopmental problems. At the present time it may be best regarded as a susceptiblity locus rather than a clinically distinct syndrome.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e The minimal deletion region is at least 1.35Mb (Mefford, 2008). The flanking regions contain a significant density of segmental duplications. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e For the total of 24 deletion patients reported by Redon and Mefford, 1q21.1 deletions were \u003ci\u003ede novo\u003c/i\u003e in 8 cases (3 with maternal origin, 2 with paternal origin, and 3 with undetermined parental origin), maternally inherited in 5, paternally inherited in 4, and of unknown inheritance in 7. The genomic structure of the 1q21.1 breakpoint regions is extremely complex with at least 4 large segmental-duplication blocks and a large inversion polymorphism that spans the recurrent deletion/duplication region. The recurrent 1.35Mb deletion/duplication occurs between breakpoints BP3 and BP4. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Andy Sharp, University of Washington, Department of Genetic Medicine and Development, University of Geneva, Switzerland\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%201/1q21.1%20Microdeletions%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK52787/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=250989\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/10813/1q211-microdeletion-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","end":147883376,"is_draft":0,"syndrome_id":62,"start":146533376,"syndrome_cnv_id":63,"updated":"2014-07-02 09:23:46.003655","genotype":"Heterozygous","created":"2012-08-01 11:20:26","chr":"1"}]}
{"CNV":[{"short_description":"2p21 Microdeletion Syndrome","assembly":"GRCh37/hg19","remap_value":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Data Awaited\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163693\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://omim.org/entry/606407\"\u003eomim.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":1,"original_position":null,"id":83,"grade":null,"remapped_from":null,"syndrome_cnv_id":83,"updated":"2014-07-02 09:23:46.245794","end":44589584,"is_draft":0,"start":44410451,"syndrome_id":87,"chr":"2","genotype":"Heterozygous","created":"2012-08-13 09:57:46"},{"remap_value":null,"short_description":"2q33.1 deletion syndrome","assembly":"GRCh37/hg19","remapped_from":null,"original_position":null,"id":50,"grade":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Severe mental retardation (microcephaly) and short stature were characteristic of the 13 patients reviewed by Van Buggenhout. All patients had a cleft or a high palate, presumably due to hemizygosity for \u003ci\u003eSATB2\u003c/i\u003e which is implicated in palate formation(Fitzpatrick).Common features were sparse thin hair, various ear anomalies and a lipodystrophy-like phenotype.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Variable, the minimum deleted region in the 4 patients described by Van Guggenhout was 8.1Mb\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e Unknown\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Thomy de Ravel, Center for Human Genetics, U.Z. Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%202/2q32%20deletions%20and%20microdeletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251028\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","syndrome_id":51,"start":196925121,"is_draft":0,"end":205206939,"updated":"2014-07-02 09:23:45.984257","syndrome_cnv_id":50,"created":"2012-07-31 15:08:26","genotype":"Heterozygous","chr":"2"},{"remap_value":null,"assembly":"GRCh37/hg19","short_description":"2p15-16.1 microdeletion syndrome","remapped_from":null,"id":69,"original_position":null,"grade":null,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Thirty three patients have been published to date and their genomic and clinical features summarized in Bagheri \u003ci\u003eet al.\u003c/i\u003e (2016). The clinical features seen in \u003e50% cases include: developmental delay and intellectual disability, language delay, feeding problems, hypotonia, microcephaly (or small head, 5–10th centile), craniofacial features (abnormal nasal root, epicanthal folds, telecanthus, ptosis, downslanting palpebral fissure, smooth and long philtrum, high, narrow palate), and distal limb anomalies (predominantly camptodactyly and/or metatarsus adductus). Structural brain abnormalities are seen in ~30% cases.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Breakpoints and the size of the deletions in the 2p15p16 region vary from ~0.1Mb (61,500,346-61,733,075) to 9.5Mb (55,676,099-65,250,541). Smallest deletions cluster in 60.5 to 62Mb region. Four genes (XPO1, BCL11A, USP34 and REL) were considered candidates based on their frequent deletion (\u003e60% cases), haploinsufficency scores and presence in the smallest deletions. Zebrafish knock-down of XPO1, BCL11A, and REL showed microcephaly and structural body anomalies. XPO1 appears to be the strongest candidate due to functional defects of nuclear transport detected in patient lymphoblasts.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e \u003ci\u003ede novo\u003c/i\u003e in all patients described to date. The deletions occurred on the maternal and paternal chromosome.\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisors:\u003c/b\u003e Dr Suzanne Lewis, Clinical Professor, Department of Medical Genetics, The University of British Columbia, Vancouver, BC Canada and Dr Evica Rajcan-Separovic, Clinical Cytogeneticist and Associate Professor, Department of Pathology, The University of British Columbia, Vancouver, BC Canada\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%202/2p15p16.1%20microdeletions%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261349\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion","syndrome_id":70,"start":59285696,"is_draft":0,"end":61819815,"updated":"2016-11-24 00:00:00","syndrome_cnv_id":69,"created":"2012-08-01 11:53:27","genotype":"Heterozygous","chr":"2"},{"remap_value":null,"short_description":"2q37 monosomy","assembly":"GRCh37/hg19","original_position":null,"grade":1,"id":44,"remapped_from":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Almost all patients have some degree of mental retardation and facial dysmorphism (round face, deep-set eyes, thin upper lip). Behavioural problems are common. Brachymetaphalangism is reported in ~50% of cases overall, but is typically not evident below the age of 2 years. There is striking phenotypic variability, and the size and extent of the deleted region cannot be used as accurate predictors of prognosis. Some patients have additional problems eg. congenital heart disease and seizures.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Variable. No common breakpoints indicating that 2q37 rearrangement is unlikely to be mediated by non-homologous recombination and low-copy repeats (Aldred). The minimum deleted region in pateints with characteristic facial dysmorphism and Albright hereditary osteodystrophy (AHO)-like brachymetaphalangism has been narrowed to ~3Mb. In Aldred's series of 20 patients, no clear relationship was found between clinical features and the size or position of the monosomic region. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e Almost all are terminal deletion. There is a high frequency of de novo deletions, but familial cases are observed. Equal proportions of maternally and paternally derived rearrangements were seen in Aldred's series.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Dr Richard Trembath, Professor of Medical Genetics, Guy's Hospital, London, UK and Dr Micheala Aldred, Senior Lecturer in Medical Molecular Genetics, University of Leicester, UK\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%202/2q37%20deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1158/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=1001&lng=EN\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"is_draft":0,"end":240322643,"start":239969863,"syndrome_id":44,"syndrome_cnv_id":44,"updated":"2014-07-02 09:23:45.975934","genotype":"Heterozygous","created":"2012-07-31 14:43:29","chr":"2"}]}
{"CNV":[{"remap_value":null,"short_description":"3q29 microdeletion syndrome","assembly":"GRCh37/hg19","original_position":null,"id":40,"grade":null,"remapped_from":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e The clinical phenotype is variable despite an almost identical deletion size. It includes mild/moderate mental retardation with mildly dysmorphic facial features (long and narrow face,short philtrum and high nasal bridge). Of the 6 reported patients, additional features eg.autism, ataxia, chest-wall deformity and long, tapering fingers were found in at least two patients in Willatt's series. Bsllif et al reviewed 14 children with insterstitial deletions of 3q29, 11 of whom had the common recurrent 1.6Mb deletion. Phenotypic features were variable, but all patients with the common recurrent deletion had mental retardation and microcephaly\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e The interstitial microdeletion is ~1.6Mb in length and encompasses 5 known genes and 17 uncharacterised transcripts.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003eThe presence of two highly homolgous LCR's in BAC clones on either side of the deletion breakpoint suggests that nonallelic homolgous recombination is the likely mechanism underlying this syndrome.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Dr F Lucy Raymond, University Lecturer, Dept of Medical Genetics, Addenbrooke's Hospital, Cambridge, UK\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%203/3q29%20deletions%20and%20microdeletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65286\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/11974/3q29-deletion-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","copy_number":1,"is_draft":0,"end":197344663,"start":195726835,"syndrome_id":37,"syndrome_cnv_id":40,"updated":"2014-07-02 09:23:45.969296","genotype":"Heterozygous","created":"2012-07-31 14:22:53","chr":"3"},{"remap_value":null,"short_description":"3q29 microduplication syndrome","assembly":"GRCh37/hg19","remapped_from":null,"original_position":null,"id":75,"grade":null,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e The clinical features of individuals with microduplications of 3q29 vary with few common features. The clinical significance of this finding remains somewhat uncertain, but in the 3-generation family described by Lisi et al, all 5 affected members of the family had mild to moderate mental retardation and microcephaly.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e Variable, with ~25% being the reciprocal of the recurrent 3q29 1.6Mb microdeletion. Although five other microduplications of 3q29 have one breakpoint that is\r\u003c/p\u003e\u003cp\u003eflanked by an LCR, only the reciprocal duplications have both breakpoints flanked by LCRs\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e The majority of 3q29 duplications in the Ballif series were inherited, with only 2/10 occurring de novo. Microduplications were inherited from either parent. This contrasts with 3q29 deletions, where the majority occur \u003ci\u003ede novo\u003c/i\u003e.\r\u003c/p\u003e\u003cp\u003eOf the 19 microduplications identified by Ballif et al, 5 were the reciprocal duplication of the common recurrent 3q29 deletion which is sponsored by LCRs of high homology and the remainder flank, span, or partially overlap the common deletion region. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003eDenise Batista, PhD, Assistant Professor, Department of Pathology, Johns Hopkins University, Baltimore, Md 21287, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups: \u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%203/3q29%20Duplications%20and%20Microduplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251038\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/10360/chromosome-3q29-microduplication-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","end":197344663,"is_draft":0,"syndrome_id":77,"start":195726835,"syndrome_cnv_id":75,"updated":"2014-07-02 09:23:46.235757","genotype":"Heterozygous","created":"2012-08-01 12:50:14","chr":"3"}]}
{"CNV":[{"short_description":"Wolf-Hirschhorn Syndrome","assembly":"GRCh37/hg19","remap_value":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cstrong\u003eClinical\u003c/strong\u003e - Characterised by low birth-weight and post-natal failure to thrive, microcephaly, developmental delay and hypotonia. There is a characteristic facial appearance with sagging everted lower eyelids, a 'Greek-helmet' profile, a short nose and very short philtrum. They may have iris colobomas. Seizures are common. Some have a visible deletion with varying breakpoints on 4p, others have a cryptic deletion requiring FISH to make the diagnosis. From Shannon's study, a minimum birth incidence of 1 in 95 896 was calculated. They found that the crude infant mortality rate was 17% (23/132) and in the first two years of life the mortality rate was 21% (28/132). Cases with large \u003cem\u003ede novo\u003c/em\u003e deletions (proximal to and including 4p15.2) were more likely to have died than those with smaller deletions.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eSize of deletion\u003c/strong\u003e - Variable, genotype-phenotype correlations in WHS mostly depend on the size of the deletion, a deletion of >3.5 Mb resulting in a mild phenotype, in which malformations are absent (Zollino). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eOrigin of deletion\u003c/strong\u003e - \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eExpert adviser:\u003c/strong\u003e \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eLinks to support groups:\u003c/strong\u003e \u003c/p\u003e\u003cp\u003e\u003ca href=\"http://wolfhirschhorn.org/\"\u003ewolfhirschhorn.org\u003c/a\u003e \u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%204/4p%20Duplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eLinks to further information:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1183/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=280\"\u003ewww.orpha.net\u003c/a\u003e \u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","original_position":null,"id":20,"grade":1,"remapped_from":null,"syndrome_cnv_id":20,"updated":"2018-03-21 16:06:28","is_draft":0,"end":2110236,"start":1569197,"syndrome_id":1,"chr":"4","genotype":"Heterozygous","created":"2012-07-31 11:11:21"}]}
{"CNV":[{"syndrome_cnv_id":34,"updated":"2014-07-02 09:23:45.94385","is_draft":0,"end":177052116,"start":175724636,"syndrome_id":17,"chr":"5","genotype":"Heterozygous","created":"2012-07-31 12:41:13","assembly":"GRCh37/hg19","short_description":"Sotos syndrome","remap_value":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Cardinal features are overgrowth from the prenatal stage through childhood; learning difficulties that can vary from very mild to severe and distinctive facial features, with large head circumference and pointed chin. Associated features, which are present in \u003e15% of cases, include advanced bone age, cardiac anomalies, renal anomalies, scoliosis and seizures. Many additional features have also been reported less frequently. Prevalence is ~1/15,000. Sotos syndrome is an AD disorder due to mutations or deletions of NSD1 (5q35). In the Japanese population ~50% of cases appear to have a common microdeletion, mediated by non-allelic homologous recombination between highly homologous sequences flanking the proximal and distal breakpoints. However, in European and American populations, microdeletions account for only 10% of cases with 83% of cases due to intragenic NSD1 mutations. The difference in microdeletion frequency may be attributable to an inversion polymorphism, involving the flanking repeats, that is common in Japan and predisposes to the microdeletion. Microdeletion cases tend to have less prominent overgrowth and more severe learning difficulties than mutation cases but all associated features of Sotos syndrome are present in both microdeletion cases and mutation cases and there is no correlation between deletion size and clinical phenotype. This suggests that deletion of additional genes in 5q35 microdeletion cases has little specific effect on phenotype. Over 90% of cases are due to `de novo' mutations, but familial cases do occur. The reasons for the low vertical transmission rate are currently unclear.\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - The common Sotos deletion is ~2Mb, but a significant proportion of deletions are of variable size, ranging from 480Kb to 5Mb.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - The majority of microdeletions (\u003e90%) arise on the paternally transmitted chromosome.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e Prof Nazneen Rahman, Honorary Consultant in Medical Genetics Section of Cancer Genetics Brookes Lawley Building Institute of Cancer Research, Sutton, Surrey, UK\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.sotossyndrome.org/\"\u003ewww.sotossyndrome.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.sssac.com/\"\u003ewww.sssac.com\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1479/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=821.0\"\u003ewww.orpha.net\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","id":34,"original_position":null,"grade":1,"remapped_from":null},{"chr":"5","genotype":"Heterozygous","created":"2012-07-31 11:21:11","syndrome_cnv_id":13,"updated":"2014-07-02 09:23:45.929044","is_draft":0,"end":12533304,"syndrome_id":2,"start":10001,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Cri du chat syndrome is characterised by a high pitched, monotonous cry, microcephaly, a round face, hypertelorism, epicanthic folds, micrognathia, impaired growth and severe developmental delay and learning disability. Comparison of phenotype with detailed molecular cytogenetic analysis suggests that the cat-like cry maps to 5p13, whereas the facial dysmorphism, microcephaly and learning disability are located on 5p15.2\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - This is very variable ranging in size from only 5p13.3 to the whole of 5p ie. ~10-45Mb. There is a progressive severity of clinical manifestations and psychomotor retardation related to increasing size of the deletion (Mainardi)\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - In Mainardi's series of 80 patients, ~80% have 'de novo' deletions (~90% of which are terminal and ~10% of which were interstitial), with ~80% arising on the paternal homologue. A further 10% arising as a result of a parental translocation and the remainder arise as a result of an unusual cytogenetic aberration. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.cridchat.u-net.com/\"\u003ewww.cridchat.u-net.com\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.genetests.org/index.php?dispatch=search.search2&search=Cri%20du%20Chat&submit=Search&start=0\"\u003ewww.genetests.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=281\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","remapped_from":null,"grade":1,"original_position":null,"id":13,"assembly":"GRCh37/hg19","short_description":"Cri du Chat Syndrome (5p deletion)","remap_value":null},{"id":49,"original_position":null,"grade":null,"remapped_from":null,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Large deletions of the APC region occur with a frequency of \u003e10% amongst mutation-negative patients with classical polyposis. Polyp numbers in deletion patients range from attenuated to profuse polyposis with significant inter- and intra-familial variability in phenotype ie. the GI phenotype appears no different from that of patients with intragenic truncating mutations. Extracolonic manifestations such as tumours of the upper gastrointestinal tract, osteomas, epidermoid cysts and desmoid tumours are common in FAP. Cytogenetically visible deletions of the APC region on 5q21 are frequently associated with mental retardation and dysmorphic features.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Deletions vary in size and occur on different haplotypes suggesting that there is no 'common' deletion\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e May arise 'de novo' or be inherited in an autosomal dominant manner\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Sabine Tejpar MD, PhD, Dept of Gastro-Enterology and Center for Human Genetics, KULeuven Belgium\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.fapsupportgroup.org\"\u003ewww.fapsupportgroup.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%205/5q%20deletions%20including%205q22%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1345/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=733&lng=EN\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","remap_value":null,"short_description":"Familial Adenomatous Polyposis","assembly":"GRCh37/hg19","created":"2012-07-31 15:02:28","genotype":"Heterozygous","chr":"5","start":112043201,"syndrome_id":49,"end":112181936,"is_draft":0,"updated":"2014-07-02 09:23:45.983307","syndrome_cnv_id":49},{"chr":"5","genotype":"Heterozygous","created":"2012-08-01 11:15:41","syndrome_cnv_id":60,"updated":"2014-07-02 09:23:46.001997","is_draft":0,"end":126172712,"start":126112314,"syndrome_id":59,"variant_class":"Duplication","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare, slowly progressive neurodegenerative condition characterised by widespread symmetrical loss of myelin in the central nervous system (CNS). The clinical picture is similar to chronic progressive multiple sclerosis (MS), indeed the clinical picture is sufficiently similar that sometimes patients are misdiagnosed as having MS. ADLD is a highly penetrant, slowly progressive disorder, usually resulting in death in the fourth or fifth decade of life. Padiath et al (2006) showed that ADLD can be caused by duplication of the gene encoding the nuclear envelope protein lamin B1 (\u003ci\u003eLMNB1\u003c/i\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e This is variable and no common breakpoint has been observed. In all three kindreds reported by Padiath, the duplication encompassed the (\u003ci\u003eLMNB1\u003c/i\u003e) gene. In one kindred, the duplication measured 340kb and in another it was 169kb.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e No low-copy repeats (LCRs) were identified flanking the duplicated region. Padiath et al postulate that the duplication may have arisen by coupled homologous and non-homologous recombination completed by non-homologous end-joining, similar to the mechanism proposed for the Pelizaeus-Merzbacher duplication.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert Advisor:\u003c/b\u003e Prof Ying-Hui Fu, Dept of Neurology, University of California at San Francisco, California, USA\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=99027\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":3,"id":60,"original_position":null,"grade":null,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"Adult-onset autosomal dominant leukodystrophy (ADLD)","remap_value":null}]}
{"CNV":[{"chr":"7","created":"2012-07-31 14:51:59","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.979213","syndrome_cnv_id":46,"start":96318078,"syndrome_id":46,"end":96339203,"is_draft":0,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Split hand/split foot malformation (SHFM, also known as ectrodactyly) is a human development disorder affecting the distal extremities. The condition is characterized by syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. The syndromic ectrodactylies (SE) are a group of human malformation syndromes that include SHFM as one component amongst a constellation of anomalies. The prototypical example of SE is the EEC (ectrodactyly, ectodermal dysphasia and cleft lip/palate) syndrome. Some SE patients also frequently suffer from hearing loss and genito-urinary anomalies. Five different genetic loci have been mapped for the isolated form of SHFM and some SE are linked to these loci; a number of isolated SHFM or SE patients are found to be associated with chromosomal rearrangement involving the 7q21.3 region (SHFM1), and families with SFHM and sensorineural hearing loss are linked to this locus. Some EEC families have been linked to 7q11.2-q21.3 (EEC1). \u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e The SHFM1 locus is an approximately 1.2-Mb critical region at 7q21.3, containing the DLX5, DLX6, and DSS1 (candidate genes). However, none of these genes are consistently interrupted by translocation/inversion breakpoints, nor has mutation in the genes been detected in sporadic or familiar SHFM patients. One possible explanation is that a position effect mutation might be involved, affecting the DLX5 and DLX6 homeobox genes since double-null knockouts of these genes in mice produce a similar phenotype. Other nearby genes could also contribute to more complex phenotype.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e SHFM is typically inherited in an autosomal dominant fashion and demonstrate a number of distinctive genetic features including reduced penetrance, variable expressivity, and segregation distortion; approximately 30% of obligate carriers of autosomal dominant SHFM show no phenotypic abnormalities (reduced penetrance). \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisors:\u003c/b\u003e Dr. Stephen W. Scherer, The Hospital for Sick Children, Toronto, Canada \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%207/7q%20deletions%20proximal%20interstitial%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2440\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/7685/split-hand-foot-malformation-1/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","id":46,"original_position":null,"grade":null,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"Split hand/foot malformation 1 (SHFM1)","remap_value":null},{"created":"2012-07-31 14:37:11","genotype":"Heterozygous","chr":"7","syndrome_id":43,"start":72744455,"is_draft":0,"end":74142672,"updated":"2014-07-02 09:23:45.974788","syndrome_cnv_id":43,"remapped_from":null,"id":43,"original_position":null,"grade":null,"copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e In the single patient described to date, the main clinical feature is severe expressive language delay (especially syntax and phonology) (Somerville). In addition he had mild growth retardation (birthweight >5th centile, height on 2nd centile, weight on 5th centile) together with subtle facial dysmorphism (high and broad nose, short philtrum. Intellectual strengths and weaknessses are in direct contrast to those typically seen in Williams-Beuren syndrome (WBS).The patient has a normal cardiovascular system.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e The duplication is the exact reciprocal of the common WBS deletion and measures ~1-5Mb and encompasses 26 or 27 genes.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e Theoretically likely to arise through interchromosomal nonallelic homologous recombination.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisers:\u003c/b\u003e Dr. Stephen W. Scherer, The Hospital for Sick Children, Toronto, Canada and Dr. Lucy Osborne, University of Toronto, Canada Nov 2005\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%207/7q%20duplications%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96121\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Duplication","remap_value":null,"assembly":"GRCh37/hg19","short_description":"7q11.23 duplication syndrome"},{"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Characteristic facial features include periorbital fullness, bulbous nasal tip, long philtrum, wide mouth, full lips, full cheeks and small widely spaced teeth. Individuals have mild to moderate intellectual disability or learning difficulties with relative cognitive strengths in verbal short term memory and in language but extreme weakness in visuospatial construction (writing, drawing, pattern construction). Distinctive behavioural characteristics include anxiety, attention deficit hyperactivity disorder (ADHD), and overfriendliness. Congenital heart disease occurs in 80%, with the majority having supravalvular aortic stenosis (SVAS), and a smaller proportion having a discrete supravalvular pulmonary stenosis. \u003c/p\u003e\u003cp\u003eThe microdeletion on 7q11.23 encompasses the elastin gene (ELN) which is also mutated in isolated SVAS. Other symptoms include hernias, visual impairment, hypersensitivity to sound, chronic otitis media, malocclusion, small or missing teeth, renal anomalies, constipation, vomiting, growth deficiency, infantile hypercalcemia, musculoskeletal abnormalities, diabetes and a hoarse voice. Risk for hypertension has been linked to the location of the distal deletion breakpoint, with hypertension being significantly less prevalent in WBS patients with a deletion that includes NCF1 (p=0.02), a gene coding for the p47phox subunit of the NADPH oxidase. This likely arises through life-long reduced angiotensin II-mediated oxidative stress. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Three large region-specific LCRs, termed centromeric, medial and telomercic, flank the WBS deletion interval. Each LCR is several hundred kb in length and is comprised of transcriptionally active genes and pseudogenes grouped into discreet blocks known as A, B and C. Most patients (\u003e95%) have a 1.55Mb deletion caused by recombination between centromeric and medial block B copies, which share approximately 99.6% nucleotide identity over many kilobases. There are at hot-spots of recombination: one within a 12 kb region of the GTF2I gene, and one in the distal end of the GTF2IRD2 gene. A few patients (>5%) have a larger deletion (~1.84Mb) caused by recombination between centromeric and medial block A copies.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Almost one-third (28%) of the transmitting progenitors are heterozygous for an inversion between centromeric and telomeric LCRs which may facilitate the deletion. The deletions are caused by nonhomologous recombination within the LCRs of either the same chromosome 7 (intrachromosomal) or different chromosome 7s (interchromosomal). In each case the chromosomes are envisaged to form loops, thereby allowing the alignment of the two LCRs, the occurrence of recombination, and the excision of the DNA contained within the intervening loop. Approximately 2/3rds of the deletion events are interchromosomal.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisors\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003eDr. Stephen W. Scherer The Hospital for Sick Children, Toronto, Canada and Dr. Lucy Osborne, University of Toronto, Canada \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.williams-syndrome.org/\"\u003ewww.williams-syndrome.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%207/7q%20deletions%20proximal%20interstitial%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1249/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=904\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","id":14,"original_position":null,"grade":1,"remapped_from":null,"short_description":"Williams-Beuren Syndrome (WBS)","assembly":"GRCh37/hg19","remap_value":null,"chr":"7","genotype":"Heterozygous","created":"2012-07-31 11:22:00","syndrome_cnv_id":14,"updated":"2014-07-02 09:23:45.931009","is_draft":0,"end":74142672,"start":72744455,"syndrome_id":3}]}
{"CNV":[{"start":77226464,"syndrome_id":86,"end":77766239,"is_draft":0,"updated":"2014-07-02 09:23:46.244884","syndrome_cnv_id":82,"created":"2012-08-01 13:20:08","genotype":"Heterozygous","chr":"8","remap_value":null,"assembly":"GRCh37/hg19","short_description":"8q21.11 Microdeletion Syndrome","id":82,"original_position":null,"grade":null,"remapped_from":null,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Data Awaited\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251076\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion"},{"is_draft":0,"end":11764629,"start":8100055,"syndrome_id":85,"syndrome_cnv_id":81,"updated":"2015-07-06 09:14:46","genotype":"Heterozygous","created":"2013-01-31 15:39:51","chr":"8","remap_value":null,"short_description":"8p23.1 duplication syndrome","assembly":"GRCh37/hg19","original_position":null,"id":81,"grade":null,"remapped_from":null,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e This genomic condition has an estimated prevalence of 1 in 58,000 (Barber \u003ci\u003eet al\u003c/i\u003e, 2013) and is the reciprocal of the 8p23.1 deletion syndrome. In seventeen probands, the duplication was de novo in ten, directly transmitted from the mother or father in four and of unknown origin in three (Barber \u003ci\u003eet al\u003c/i\u003e, 2013; Yu \u003ci\u003eet al\u003c/i\u003e, 2011; Barber \u003ci\u003eet al\u003c/i\u003e, 2010; Yu \u003ci\u003eet al\u003c/i\u003e, 2010; Barber \u003ci\u003eet al\u003c/i\u003e, 2008; Barber \u003ci\u003eet al\u003c/i\u003e, 2005). Common features include mild or moderate developmental delay and/or learning difficulties in 11/12 postnatal probands, a variable degree of mild dysmorphism in 8/12 (which may be limited to a prominent forehead and/or arched eyebrows) and congenital heart disease (CHD) in 4/5 prenatal and 3/12 postnatal probands. Additional features in a proportion of patients include behavioral problems, cleft lip and/or palate, macrocephaly, seizures, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia and hydrocele (Barber\u003c/i\u003e et al\u003c/i\u003e, 2013). The phenotype is compatible with independent adult life with varying degrees of support. Many features are common to both the 8p23.1 deletion and duplication syndromes (Ballarati \u003ci\u003eet al\u003c/i\u003e, 2011) but may have lower penetrance in the 8p23.1 duplication syndrome; for instance, congenital diaphragmatic hernia (CDH) has been found many times in patients with 8p23.1 deletions but only once in a patient with the 8p23.1 duplication syndrome to date (Longoni \u003ci\u003eet al\u003c/i\u003e, 2012, Patient 3).\u003c/p\u003e\u003cp\u003eThe core duplication of 3.68 Mb contains thirty-one genes and microRNAs but microduplications within this region suggest that many of the features of 8p23.1 duplication syndrome result from a 776 kb interval of 8p23.1 (chr8:10,167,881-10,943,836 hg19) that contains only eight genes including the SOX7 transcription factor (OMIM *612202) (Barber \u003c/i\u003eet al\u003c/i\u003e, 2015). SOX7 in medial 8p23.1 is a strong candidate for intellectual disability and dysmorphism as well as a potential modifier of CHD (Barber \u003ci\u003eet al\u003c/i\u003e, 2015; Wat \u003ci\u003eet al\u003c/i\u003e, 2009; Paez \u003ci\u003eet al\u003c/i\u003e, 2008). The GATA4 transcription factor (OMIM *600576) in centromeric 8p23.1 is the outstanding candidate for the conotruncal and septal heart defects (Barber \u003ci\u003eet al\u003c/i\u003e, 2013; Barber \u003ci\u003eet al\u003c/i\u003e, 2010; Yu \u003ci\u003eet al\u003c/i\u003e, 2010; Barber \u003ci\u003eet al\u003c/i\u003e, 2005). It is possible that the 8p23.1 duplication syndrome is an oligogenetic condition resulting largely from the duplication and interactions of the SOX7 and GATA4 transcription factors (Barber \u003ci\u003eet al\u003c/i\u003e, 2015).\u003c/p\u003e\u003cp\u003eThe duplication may involve copy number changes of the adjacent olfactory receptor/defensin repeats (ORDRs) that have been associated with a number of traits. The association between increasing total copy number and higher predisposition to psoriasis Hollox \u003ci\u003eet al\u003c/i\u003e, 2008a) has been substantiated (Stuart \u003c/i\u003eet al\u003c/i\u003e, 2012;) but that of low or high copy number with predisposition to Crohns disease (Fellermann \u003ci\u003eet al\u003c/i\u003e, 2006) has not (Aldhous \u003ci\u003eet al\u003c/i\u003e, 2010).\u003c/p\u003e\u003cp\u003ePlease note: the phenotype associated with the well-known inverted duplications of 8p (inv dup del(8)s) is not relevant as the duplicated region in the 8p23.1 duplication syndrome is specifically not duplicated in the inv dup del(8) rearrangements (Giglio \u003ci\u003eet al\u003c/i\u003e, 2001).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e : ~ 3.68 Mb between the distal and proximal olfactory receptor/defensin repeats (ORDRs) at the telomeric and centromeric ends of band 8p23.1. The copy number of the adjacent repeats may also be altered and occasional duplications involve limited regions beyond the repeats.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePlease note: the 8p23.1 duplication syndrome cannot be distinguished using conventional cytogenetics from high level copy number variation of the repeats themselves (Barber \u003ci\u003eet al\u003c/i\u003e, 2010; Barber \u003ci\u003eet al\u003c/i\u003e, 2005).\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e both de novo cases and families with transmitted duplications from parents of both sexes are known. The duplication is believed to arise de novo as a result of non-allelic homologous recombination (NAHR) between the proximal and distal olfactory receptor/defensin repeats (ORDRs) (Giglio \u003ci\u003eet al\u003c/i\u003e, 2001). NAHR is also thought to give rise to the reciprocal microdeletion syndrome, the polymorphic inversion between the ORDRs and a variety of other large scale abnormalities involving the short arm of chromosome 8 (Hollox \u003ci\u003eet al\u003c/i\u003e, 2008b).\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert Advisor:\u003c/b\u003e Dr John Barber, Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%208/8p23%20duplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251076\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"chr":"8","genotype":"Heterozygous","created":"2012-07-31 14:29:04","syndrome_cnv_id":41,"updated":"2014-07-02 09:23:45.972004","end":11764629,"is_draft":0,"syndrome_id":39,"start":8100055,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e A recently defined microdeletion syndrome characterised by congenital heart disease, congenital diaphragmatic hernia, developmental delay and a characteristic behaviour profile with hyperactivity and impulsiveness. The congenital heart disease charachteristic of this deletion is attributable to haploinsufficiency for the gene \u003ci\u003eGATA4\u003c/i\u003e. To date, the literature describes an association between congenital diaphragmatic hernia and 8p23.1 deletion in 4 cases (Shimokawa). \u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Some interstitial deletions have a consistent size of ~3.4 Mb (eg. Shimokawa). Some deletions are larger than this and may even extend to include the 8p telomere (Devriendt).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e All cases reported to date are \u003ci\u003ede novo\u003c/i\u003e. The deletion is likely to arise through non-allelic homologous recombination sponsored by flanking low-copy repeats (LCRs). \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser: \u003c/b\u003eDr Koen Devriendt, Centrum Menselijke Erfelijkheid, Herestraat 49 B-3000, Leuven, Belgium \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%208/8p23%20Deletions%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251071\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/GARD/Condition/3769/Chromosome_8p231_deletion.aspx\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","copy_number":1,"remapped_from":null,"original_position":null,"id":41,"grade":null,"assembly":"GRCh37/hg19","short_description":"8p23.1 deletion syndrome","remap_value":null}]}
{"CNV":[{"chr":"9","genotype":"Heterozygous","created":"2012-07-31 15:15:41","syndrome_cnv_id":61,"updated":"2014-07-02 09:23:45.986409","end":140730578,"is_draft":0,"start":140513443,"syndrome_id":52,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Patients with a cryptic del(9)(q34.3) have a clinically recognizable phenotype characterised by severe developmental delay/learning disability, hypotonia, microcephaly, congenital heart disease (especially conotruncal defects), seizures (in ~30%) and a distinctive facial gestalt. The craniofacial features include arched eyebrows with synophrys, hypertelorism, short nose with anteverted nares, open mouth appearance and protruding tongue. The gene \u003ci\u003eEHMT1\u003c/i\u003e appears to be responsible for the craniofacial features, microcephaly, hypotonia and developmental delay (Kleefstra). \u003ci\u003eEHMT1\u003c/i\u003e is widely expressed and is involved in chromatin modification leading to transcriptional silencing of genes. \u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Deletions vary in size from ~0.7Mb to 2.3Mb. Despite the fact that this is a not infrequent subtelomeric deletion syndrome, there do not appear to be any common breakpoints nor have architectural features sponsoring deletions in this region been identified. There appears to be a positive correlation between deletion size and phenotypic severity ie. those with larger deletions have a more severe phenotype.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Svetlana Yatsenko, MD, Dept of Molecular and Human Genetics, Baylor College Medicine, Houston, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%20%209/Kleefstra%20Syndrome%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK47079/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96147\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"grade":1,"original_position":null,"id":61,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"9q subtelomeric deletion syndrome","remap_value":null}]}
{"CNV":[{"is_draft":0,"end":46052450,"syndrome_id":34,"start":43994800,"syndrome_cnv_id":39,"updated":"2014-07-02 09:23:45.966301","genotype":"Heterozygous","created":"2012-07-31 14:17:35","chr":"11","remap_value":null,"assembly":"GRCh37/hg19","short_description":"Potocki-Shaffer syndrome","remapped_from":null,"id":39,"original_position":null,"grade":1,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - The clinical features of PSS can include developmental delay, mental retardation, multiple exostoses, parietal foramina, enlarged anterior fontanel, minor craniofacial anomalies, ophthalmologic anomalies, and genital abnormalities in males.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - The deletion is of variable size. The full spectrum of PSS manifests when deletions are at least 2.1 Mb in size, encompassing EXT2, responsible for multiple exostoses, and ALX4, causing parietal foramina.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=52022\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/GARD/Condition/9762/PotockiShaffer_syndrome.aspx\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e"},{"genotype":"Heterozygous","created":"2012-07-31 14:20:06","chr":"11","is_draft":0,"end":32457087,"start":31806339,"syndrome_id":35,"syndrome_cnv_id":76,"updated":"2014-07-02 09:23:45.967476","original_position":null,"grade":null,"id":76,"remapped_from":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Wilms tumor, Aniridia, Genitourinary abnormalities, growth and mental Retardation are the cardinal features of the WAGR 11p13 deletion syndrome. This is a rare disorder with an estimated prevalence of ~1 in 500,000 to 1 per million. Children with WAGR syndrome should receive regular (3-4 monthly) renal surveillance for Wilm's tumour until at least the age of 6-8 years and thereafter should remain under some renal follow-up because of the risk of late onset nephropathy (40% of patients over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase their risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present. \u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - These are of variable size (eg. 1-26.5Mb)but always include the genes \u003ci\u003eWT1\u003c/i\u003e and \u003ci\u003ePAX6\u003c/i\u003e that account for the common oncogenic (\u003ci\u003eWT1\u003c/i\u003e), ocular and genitourinary features (\u003ci\u003ePAX6\u003c/i\u003e) of the syndrome. People with WAGR syndrome typically have low-normal birthweight, but a substantial proportion subsequently develop marked obesity. Han (2008) demonstrated that the obese individuals were likely to be deleted for the brain-derived neurotrophic factor (\u003ci\u003eBDNF\u003c/i\u003e)further implicating this gene, which encodes a component of the leptin signalling pathway, in energy homeostasis as initially suggested by Gray (2006).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Most cases of WAGR syndrome are identified in infants with sporadic aniridia, 30% of whom will be positive for the characteristic deletion (11p13).\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Joan C. Han, MD, Senior Clinical Fellow in Pediatric Endocrinology Unit on Growth and Obesity Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, MD, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.wagr.org\"\u003ewww.wagr.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=893&lng=EN\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/GARD/Condition/5528/WAGR_syndrome.aspx\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","copy_number":1,"remap_value":null,"assembly":"GRCh37/hg19","short_description":"WAGR 11p13 deletion syndrome"}]}
{"CNV":[{"remap_value":null,"assembly":"GRCh37/hg19","short_description":"12q14 microdeletion syndrome","original_position":null,"id":74,"grade":null,"remapped_from":null,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e The three children reported by Menten et al all had a similar and characteristic phenotype consisting of mild mental retardation, failure to thrive in infancy, proportionate short stature and osteopoikilosis. The common 3.44Mb deleted region contains the \u003ci\u003eLEMD3\u003c/i\u003e gene. Loss of function mutations in this gene cause osteopoikilosis and the Bushke-Ollendorff syndrome (BOS). \u003ci\u003eLEMD3\u003c/i\u003e mutations have also been identified in melorheostosis patients who belong to a family with BOS but they are rarely present in sporadic melorheostosis\u003c/p\u003e\u003cp\u003eFailure to thrive, short stature and mental retardation are not observed in patients with osteopoikilosis or melorheostosis and these features are presumed to be attributable to another dosage sensitive gene(s) in the common deleted region.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Variable deletion size, varying between 3.44 and 6 Mb in size with a 3.44 Mb common deleted region.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e The deletion occurred as a \u003ci\u003ede novo\u003c/i\u003e event. The breakpoints are variable and apparently non-recurrent. Given the apparent absence of low copy repeats\r\u003c/p\u003e\u003cp\u003enear the 12q breakpoints described here, a mechanism of non-homologous end-joining (NHEJ) may be responsible for the occurrence of the microdeletions in the three published cases\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Geert Mortier, Department of Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2012/12q14%20microdeletion%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=94063&Lng=EN\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/1044/buschke-ollendorff-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion","start":65071919,"syndrome_id":76,"is_draft":0,"end":68645525,"updated":"2014-07-02 09:23:46.234071","syndrome_cnv_id":74,"created":"2010-03-09 11:22:14","genotype":"Heterozygous","chr":"12"},{"updated":"2014-07-02 09:23:46.249486","syndrome_cnv_id":87,"start":1080000,"syndrome_id":91,"end":1346471,"is_draft":0,"chr":"12","created":"2012-09-26 16:17:54","genotype":"Heterozygous","assembly":"GRCh37/hg19","short_description":"12p13.33 Microdeletion Syndrome","remap_value":null,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Data Awaited\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","variant_class":"Deletion","original_position":null,"id":87,"grade":null,"remapped_from":null}]}
{"CNV":[{"remapped_from":null,"grade":1,"original_position":null,"id":17,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - The most common recognised genetic form of obesity affecting 1/10,000 - 15,000 individuals. Babies have central hypotonia and feeding difficulties with failure to thrive in infancy. There is rapid weight gain between the ages 1-6yrs (usually 2-4yrs), characterised by truncal obesity with small hands & feet, strikingly fat limbs, small genitalia in males, and short stature. Typically there is insatiable appetite and food seeking/hoarding. Most patients have IQ 60s-low 70s, approx 40% have borderline retardation or low normal intelligence, and 20% have moderate retardation. Overall the IQ of a populations based sample of PWS patients is normally distributed with a mean IQ of 60, with parental and social factors accounting for the distribution as they do in the general population. Individuals with PWS are often good at jigsaws and word-find puzzles. Behavioural problems can be a major issue and 80% have some ritualistic behaviours (Holland). Most adults with PWS will require support/supervision in adult life and few will live independently. Both males & females have hypogonadotrophic hypogonadism, sexual activity is uncommon and fertility is rare (but note if deletion, girls are at 50% risk for child with Angelman syndrome - birth of an AS child to a PWS mother has been reported by Schulze).\u003c/p\u003e\u003cp\u003eApproximately 70-75% of patients with PWS have del 15q11-13, 20-25% have UPD 15mat, and only 1-3% have an imprinting defect (abnormal DNA methylation but normal FISH and UPD studies). \u003ci\u003eSNRPN\u003c/i\u003e DNA methylation analysis detects PWS in greater than 99% of cases irrespective of the molecular class.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Deletional PWS typically result from an approximately 4-Mb deletion of human chromosome 15q11-q13, with clustered breakpoints (BP) at either of two proximal sites (BP1 for type 1 and BP2 for Type 2) and one distal site (BP3) (Chai).\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - The deletion arises on the paternal homologue. Due to imprinting, the maternally inherited genes in the PWS critical region of 15q11.2 are usually inactive and normal development is dependent upon the paternally inherited active genes. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Suzanne B. Cassidy, M.D., Univ. California Dept. Pediatrics, Sausalito, CA 94965 USA and Daniel J. Driscoll, M.D., Ph.D., Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://pwsa.co.uk\"\u003epwsa.co.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.pwsausa.org/\"\u003ewww.pwsausa.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.praderwillisyndrome.org.uk/\"\u003ewww.praderwillisyndrome.org.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/15q%20Deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1330/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=739\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","variant_class":"Deletion","remap_value":null,"short_description":"Prader-Willi syndrome (Type 1)","assembly":"GRCh37/hg19","created":"2012-07-31 12:23:00","genotype":"Heterozygous","chr":"15","syndrome_id":14,"start":22749354,"end":28438266,"is_draft":0,"updated":"2014-07-02 09:23:45.938227","syndrome_cnv_id":17},{"syndrome_cnv_id":66,"updated":"2014-07-02 09:23:46.224047","end":75972911,"is_draft":0,"start":74412643,"syndrome_id":66,"chr":"15","genotype":"Heterozygous","created":"2012-08-01 11:38:12","assembly":"GRCh37/hg19","short_description":"15q24 recurrent microdeletion syndrome","remap_value":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e 15q24 microdeletion syndrome is a newly defined syndrome (2007). Of the four patients described to date (Sharp) all had mild mental retardation (IQ 60-70), together with growth retardation, microcephaly, digital abnormalities, hypospadias (3/4) and loose connective tissue. A degree of facial resemblence was noted with high anterior hair line, broad medial eyebrows, hypertelorism, downslanted palpebral fissures, broad nasal base, long smooth philtrum and full lower lip.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e 1-7-3.9Mb. In Sharp's series, high-resolution analysis showed that in three patients both proximal and distal breakpoints co-localized to highly identical segmental duplications, suggesting non-allelic homologous recombination (NAHR) as the likely mechanism of origin.However,in a fourth case, which was clinically indistinguishable, both proximal and distal breakpoints were located in unique sequence. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e The majority of cases observed to date appear due to \u003ci\u003ede novo\u003c/i\u003e deletions. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Andy Sharp, University of Washington, Dept. of Genome Sciences, Seattle, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/15q%20Deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK84258/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=94065&lng=EN\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"original_position":null,"grade":null,"id":66,"remapped_from":null},{"end":28438266,"is_draft":0,"syndrome_id":4,"start":22749354,"syndrome_cnv_id":18,"updated":"2014-07-02 09:23:45.933621","genotype":"Heterozygous","created":"2012-07-31 11:25:23","chr":"15","remap_value":null,"short_description":"Angelman syndrome (Type 1)","assembly":"GRCh37/hg19","remapped_from":null,"original_position":null,"id":18,"grade":1,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Angelman syndrome (AS) is a distinctive neurobehavioural disorder resulting from disruption to the function of the maternally derived imprinted domain on 15q11.13 (more specifically UBE3A). It affects ~1/40,000 children. Patients with classical Angelman syndrome (AS) exhibit: (i)Severe developmental delay (ii)Profound speech impairment - many do not acquire speech, at the very most >3-4 words. Receptive and non-verbal communication skills are significantly better than expressive skills. Most children with AS use gesture to communicate and some are able to use sign language (eg. Makaton, PECS) (iii)A movement and balance disorder - ataxic gait (iv)Specific behaviour with excitable personality and inappropriately happy affect. Other features include microcephaly, hypopigmentation (in some deletion patients) and seizures. The EEG typically shows 2-3Hz large amplitude slow wave bursts. The EEG may be abnormal even if there is no history of seizures; however a normal EEG does not exclude the diagnosis\u003c/p\u003e\u003cp\u003eAS is caused by defects in the maternally derived imprinted domain on 15q11.13 which can arise in a variety of ways. Interstitial deletion of 15q11-13mat is the most common type accounting for 70% of cases. Paternal UPD 15 (2-5%), an imprinting defect (2-5%), or mutation in the E3 ubiquitin protein ligase gene (UBE3A) (5-10%) are other mechanisms and in a small percentage the molecular mechanism is currently unidentified. All patients with an interstitial deletion, UPD or an imprinting defect ie. ~80% in total will have an SNRPN methylation abnormality (only unmethylated alleles). Normal individuals will show one methylated (maternal) and one unmethylated (paternal) allele. Patients with UBE3A mutations, AS of unidentified cause, and those with a phenocopy of AS but a different disorder will all show normal results on the SNRPN methylation assay.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Angelman syndrome typically result from an approximately 4-Mb deletion of human chromosome 15q11-q13, with clustered breakpoints (BP) at either of two proximal sites (BP1 for type 1 and BP2 for Type 2) and one distal site (BP3).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Deletions arise on the maternal homologue. [Deletions of the PWS/AS critical region which arise on the paternal homologue cause Prader-Willi syndrome.] The great majority of deletions of the PWS/AS critical region arise \u003ci\u003ede novo\u003c/i\u003e.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e Dr Jill Clayton-Smith, Consultant Clinical Geneticist, St Mary's Hospital, Manchester, UK\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.angelman.org/\"\u003ewww.angelman.org\u003c/a\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.angelmanuk.org/\"\u003ewww.angelmanuk.org\u003c/a\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.angelman.org/\"\u003ewww.angelman.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.asclepius.com/iaso/\"\u003ewww.asclepius.com\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/15q%20Deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1144/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=72\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":1},{"remapped_from":null,"original_position":null,"id":72,"grade":null,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e This microdeletion syndrome was first described by Sharp et al in 2008 and is characterised by developmental delay with mild/moderated learning disability, seizures and subtle facial dysmorphism. A high percentage of patients have minor hand anomalies eg. short 4th metacarpal or 5th finger clinodactyly. Expressivity of the condition appears to be quite variable. There is no striking facial gestalt and given the lack of distinctive features in the phenotype, this is unlikely to become a disorder which is easily recognisable clinically. \u003c/p\u003e\u003cp\u003eThe seizure disorder is variable; 7 of the 9 patients in Sharp's series had seizures or an abnormal EEG. The seizures varied from absence seizures to generalised tonic-clonic seizures to myoclonic epilepsy. One patient had intractable epilepsy. The deletion encompasses \u003ci\u003eCHRNA7\u003c/i\u003e(cholinergic receptor, neuronal nicotinic, alpha polypeptide 7), a synaptic ion channel protein that mediates neuronal signal transmission.\r\u003c/p\u003e\u003cp\u003eSharp et al estimate an approximate population incidence of ~1/40,000. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e There is a shared 1.5 Mb region between segmental duplications at BP4 and BP5 containing six known genes. Although they occur more rarely, there is also a larger recurrent deletion between BP3 and BP5 associated with this phenotype\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e This region of chromosome 15q containes a complex set of segmental duplications, termed duplication blocks (eg. BP4). The BP4 and BP5 are in inverted orientation in a proportion of individuals in the general population which facilitates non-homologous recombination of this region at meiosis. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Evan Eichler, Department of Genome Sciences, University of Washington and Howard Hughes Medical Institute, Seattle, Washington, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/15q13.3%20microdeletion%20syndrome%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK50780/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=199318\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion","remap_value":null,"short_description":"15q13.3 microdeletion syndrome","assembly":"GRCh37/hg19","created":"2012-08-06 12:42:38","genotype":"Heterozygous","chr":"15","syndrome_id":74,"start":30910306,"end":32445407,"is_draft":0,"updated":"2014-07-02 09:23:46.232229","syndrome_cnv_id":72},{"genotype":"Heterozygous","created":"2010-03-09 11:25:19","chr":"15","end":102521392,"is_draft":0,"syndrome_id":81,"start":99357970,"syndrome_cnv_id":80,"updated":"2014-07-02 09:23:46.241878","remapped_from":null,"id":80,"original_position":null,"grade":null,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Renal anomalies occur in ~45% and include horseshoe kidney, renal agenesis,\u003c/p\u003e\u003cp\u003ehydronephrosis, vesico-ureteric reflux,polycystic kidney and right renal pelvic duplication.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003cb\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/Duplications%20of%2015q%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","remap_value":null,"short_description":"15q26 overgrowth syndrome","assembly":"GRCh37/hg19"},{"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Angelman syndrome (AS) is a distinctive neurobehavioural disorder resulting from disruption to the function of the maternally derived imprinted domain on 15q11.13 (more specifically UBE3A). It affects ~1/40,000 children. Patients with classical Angelman syndrome (AS) exhibit: (i)Severe developmental delay (ii)Profound speech impairment - many do not acquire speech, at the very most >3-4 words. Receptive and non-verbal communication skills are significantly better than expressive skills. Most children with AS use gesture to communicate and some are able to use sign language (eg. Makaton, PECS) (iii)A movement and balance disorder - ataxic gait (iv)Specific behaviour with excitable personality and inappropriately happy affect. Other features include microcephaly, hypopigmentation (in some deletion patients) and seizures. The EEG typically shows 2-3Hz large amplitude slow wave bursts. The EEG may be abnormal even if there is no history of seizures; however a normal EEG does not exclude the diagnosis\u003c/p\u003e\u003cp\u003eAS is caused by defects in the maternally derived imprinted domain on 15q11.13 which can arise in a variety of ways. Interstitial deletion of 15q11-13mat is the most common type accounting for 70% of cases. Paternal UPD 15 (2-5%), an imprinting defect (2-5%), or mutation in the E3 ubiquitin protein ligase gene (UBE3A) (5-10%) are other mechanisms and in a small percentage the molecular mechanism is currently unidentified. All patients with an interstitial deletion, UPD or an imprinting defect ie. ~80% in total will have an SNRPN methylation abnormality (only unmethylated alleles). Normal individuals will show one methylated (maternal) and one unmethylated (paternal) allele. Patients with UBE3A mutations, AS of unidentified cause, and those with a phenocopy of AS but a different disorder will all show normal results on the SNRPN methylation assay.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Deletional AS typically result from an approximately 4-Mb deletion of human chromosome 15q11-q13, with clustered breakpoints (BP) at either of two proximal sites (BP1 for type 1 and BP2 for Type 2) and one distal site (BP3).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Deletions arise on the maternal homologue. [Deletions of the PWS/AS critical region which arise on the paternal homologue cause Prader-Willi syndrome.] The great majority of deletions of the PWS/AS critical region arise \u003ci\u003ede novo\u003c/i\u003e.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e Dr Jill Clayton-Smith, Consultant Clinical Geneticist, St Mary's Hospital, Manchester, UK\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.angelman.org/\"\u003ewww.angelman.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.angelmanuk.org/\"\u003ewww.angelmanuk.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.angelman.org/\"\u003ewww.angelman.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.asclepius.com/iaso/\"\u003ewww.asclepius.com\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/15q%20Deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1144/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=72\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion","id":54,"original_position":null,"grade":1,"remapped_from":null,"short_description":"Angelman syndrome (Type 2)","assembly":"GRCh37/hg19","remap_value":null,"chr":"15","created":"2012-07-31 15:19:23","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.990365","syndrome_cnv_id":54,"start":23619912,"syndrome_id":54,"end":28438266,"is_draft":0},{"id":53,"original_position":null,"grade":1,"remapped_from":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - The most common recognised genetic form of obesity affecting 1/10,000 - 15,000 individuals. Babies have central hypotonia and feeding difficulties with failure to thrive in infancy. There is rapid weight gain between the ages 1-6yrs (usually 2-4yrs), characterised by truncal obesity with small hands & feet, strikingly fat limbs, small genitalia in males, and short stature. Typically there is insatiable appetite and food seeking/hoarding. Most patients have IQ 60s-low 70s, approx 40% have borderline retardation or low normal intelligence, and 20% have moderate retardation. Overall the IQ of a populations based sample of PWS patients is normally distributed with a mean IQ of 60, with parental and social factors accounting for the distribution as they do in the general population. Individuals with PWS are often good at jigsaws and word-find puzzles. Behavioural problems can be a major issue and 80% have some ritualistic behaviours (Holland). Most adults with PWS will require support/supervision in adult life and few will live independently. Both males & females have hypogonadotrophic hypogonadism, sexual activity is uncommon and fertility is rare (but note if deletion, girls are at 50% risk for child with Angelman syndrome - birth of an AS child to a PWS mother has been reported by Schulze).\u003c/p\u003e\u003cp\u003eApproximately 70-75% of patients with PWS have del 15q11-13, 20-25% have UPD 15mat, and only 1-3% have an imprinting defect (abnormal DNA methylation but normal FISH and UPD studies). \u003ci\u003eSNRPN\u003c/i\u003e DNA methylation analysis detects PWS in greater than 99% of cases irrespective of the molecular class.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Deletional PWS typically result from an approximately 4-Mb deletion of human chromosome 15q11-q13, with clustered breakpoints (BP) at either of two proximal sites (BP1 and BP2) and one distal site (BP3) (Chai).\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - The deletion arises on the paternal homologue. Due to imprinting, the maternally inherited genes in the PWS critical region of 15q11.2 are usually inactive and normal development is dependent upon the paternally inherited active genes. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Suzanne B. Cassidy, M.D., Univ. California Dept. Pediatrics, Sausalito, CA 94965 USA and Daniel J. Driscoll, M.D., Ph.D., Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003ePrader-Willi Association (UK) \u003ca href=\"http://www.pwsa.org.uk/\"\u003ewww.pwsa.org.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003ePrader-Willi Syndrome Association (US) \u003ca href=\"http://www.pwsausa.org/\"\u003ewww.pwsausa.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.praderwillisyndrome.org.uk/\"\u003ewww.praderwillisyndrome.org.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2015/15q%20Deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1330/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=739\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","remap_value":null,"assembly":"GRCh37/hg19","short_description":"Prader-Willi Syndrome (Type 2)","genotype":"Heterozygous","created":"2012-07-31 15:19:01","chr":"15","is_draft":0,"end":28438266,"start":23619912,"syndrome_id":53,"syndrome_cnv_id":53,"updated":"2014-07-02 09:23:45.988509"}]}
{"CNV":[{"start":29606852,"syndrome_id":78,"is_draft":0,"end":30199855,"updated":"2014-07-02 09:23:46.237121","syndrome_cnv_id":77,"created":"2012-08-01 12:54:31","genotype":"Heterozygous","chr":"16","remap_value":null,"assembly":"GRCh37/hg19","short_description":"16p11.2 microduplication syndrome","original_position":null,"id":77,"grade":null,"remapped_from":null,"copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Deletions and duplications at chromosome 16p11.2 appear to be associated with ~1% of unexplained, idiopathic and nonsyndromic autism. Developmental regression which affects ~40% of children with late-onset autism was not seen in Weiss' study indicating that 16p11.2 deletion or duplication events are mostly associated with autism of early onset. The penetrance of autism in individuals with this deletion is unknown since in Weiss studied families with autism. Indeed there is a suggestion that autism is not an obligatory consequence of this deletion since a case report by Ghebranious describes a child with the same deletion who had aortic valve disease, seizures and mild mental retardation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion/duplication:\u003c/b\u003e The deletion measures ~600kb and the breakpoints appeared identical in all 8 children studied by Weiss and the same as for the 11 individuals with the duplication. There are more than 25 genes or transcripts in the critical interval as well as rapidly evolving genes in the flanking duplications.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion/duplication:\u003c/b\u003e Of the 13 indiviudals reported by Weiss, the rearrangements arose \u003ci\u003ede novo\u003c/i\u003e in 10, was inheirted from parents with ADHD or mental retardation in 2 and was unkown in one. Interspersed duplicaion blocks (12 and 13) on 16p11.2 promote unequal crossing over during meiosis (NAHR). \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p11.2%20microduplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=261204\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","variant_class":"Duplication"},{"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e Variable in size \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e Usually arises \u003ci\u003ede novo\u003c/i\u003e or as the unbalanced product of a reciprocal translocation\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p13%20deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1435/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98791\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/621/alpha-thalassemia/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","copy_number":1,"id":65,"original_position":null,"grade":1,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"ATR-16 syndrome","remap_value":null,"chr":"16","genotype":"Heterozygous","created":"2010-03-09 11:35:13","syndrome_cnv_id":65,"updated":"2014-07-02 09:23:46.221931","is_draft":0,"end":834372,"start":60001,"syndrome_id":65},{"chr":"16","created":"2012-08-01 12:58:29","genotype":"Heterozygous","updated":"2014-07-02 09:23:46.238486","syndrome_cnv_id":78,"syndrome_id":79,"start":14986684,"end":16486684,"is_draft":0,"description":"\u003cp\u003e\u003cb\u003eClinical: \u003c/b\u003e A recurrent 1.5Mb microdeletion was first observed by Ullmann et al (2007) in 3 unrelated individuals with MR and subsequently by Hannes et al (2008) who used a BAC array CGH screen of 1027 individuals with mental retardation (MR) and/or multiple congenital anomalies (MCA). Using this approach, recurrent deletions of 16p13.11 were observed in 5 individuals and overlapping or flanking deletions were seen in a further 3 individuals. In comparison, no deletions were observed amongst a control population of \u003e2000 normal individuals (p>0.005). Unfortunately trio analysis was undertaken for only one patient with a recurrent deletion and in this instance showed that the deletion was inherited from a phenotypically normal father. Furthermore, the phenotype in the 5 cases was variable with the 3 postnatal cases all having moderate/severe MR, with epilepsy in 2 of the 3. The 2 antenatally diagnosed cases had structural brain anomalies, holoprosencephaly in one and ventriculomegaly in the other with additional, but varying, congenital anomalies. Overall, it seems more likely that this is a susceptibility locus for neurocognitive disease than that 16p13.11 deletion is in itself sufficient to cause the phenotype, but further data is needed before reaching a definitive conclusion.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion: \u003c/b\u003eThe recurrent deletion measures 1.65 Mb and enecompasses ~15 genes. There is a reciprocal duplication.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion: \u003c/b\u003eThe deletion is likely to be sponsored by highly homologous repeat sequences (LCR16's). Chromosome 16 is particuarly rich in these elements.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor: \u003c/b\u003e Dr Thomy JL de Ravel, Centre for Medical Genetics, UZ Leuven, Leuven, Belgium\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups: \u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p13.11%20microdeletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261236\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","remapped_from":null,"grade":null,"original_position":null,"id":78,"short_description":"16p13.11 recurrent microdeletion (neurocognitive disorder susceptibility locus)","assembly":"GRCh37/hg19","remap_value":null},{"short_description":"16p11.2-p12.2 microdeletion syndrome","assembly":"GRCh37/hg19","remap_value":null,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Ballif et al. reported four indiivduals with \u003ci\u003ede novo\u003c/i\u003e deletions of 16p11.2-p12.2 identified by genomic array analysis. They had subtly dysmorphic facial features including flat facies, downslanting palpebral fissures, low-set ears and eye anaomalies. All had developmental delay/mental retardation. \u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e The deletion shared a common distal breakpoint, but variable proximal breakpoints. The deletion size ranged from 7.1Mb-8.7Mb.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e 16p11.2-p12.2 has a complex arrangement of segmental duplications, some of which directly flanked the deletion breakpoints. The location and orientation of the segmental duplications suggest that nonallelic homologous recombination (NAHR) is the mechanism underlying these \u003ci\u003ede novo\u003c/i\u003e deletions.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p11.2%20microdeletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK11167/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=261197\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","remapped_from":null,"original_position":null,"id":68,"grade":null,"updated":"2014-07-02 09:23:46.227249","syndrome_cnv_id":68,"syndrome_id":68,"start":21512062,"end":30199854,"is_draft":0,"chr":"16","created":"2012-08-01 11:45:39","genotype":"Heterozygous"},{"syndrome_cnv_id":79,"updated":"2014-07-02 09:23:46.240358","end":16486684,"is_draft":0,"syndrome_id":80,"start":14986684,"chr":"16","genotype":"Heterozygous","created":"2012-08-01 12:59:53","assembly":"GRCh37/hg19","short_description":"16p13.11 recurrent microduplication (neurocognitive disorder susceptibility locus) ","remap_value":null,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical: \u003c/b\u003e Ullmann et al 2007 first reported an apparent association between this duplication and autism.In the study by Hannes 2008, recurrent reciprocal duplications were found in similar frequency in a population of \u003e2000 patients with mental retardation/multiple congenital anomalies (MR/MCA)and a control population.However when Mefford et al undertook a study of \u003e1000 children with unexplained intellectual disability, they found 1.65-3.4 Mbp duplications at 16p13.11 in 1.1% of affected individuals with this CNV significantly enriched in this cohort compared with controls.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication: \u003c/b\u003e The recurrent duplication measures 1.65 Mb and encompasses ~15 genes. There is a reciprocal deletion with identical breakpoints that is also thought to be a susceptibility locus for neurognitive disease suggesting that there is a dosage sensitive gene(s) affecting brain development in this interval. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication: \u003c/b\u003e The duplication is likely to be sponsored by highly homologous repeat sequences (LCR16's). Chromosome 16 is particuarly rich in these elements. In the patients reported by Hannes duplications were observed as both inherited and \u003ci\u003ede novo\u003c/i\u003e events. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert Advisor: \u003c/b\u003eProfessor K Devriendt, Centre for Human Genetics, Herestraat 49, Leuven B-3000, Belgium.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups: \u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p13.11%20microduplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261243\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","remapped_from":null,"id":79,"original_position":null,"grade":null},{"remap_value":null,"short_description":"16p11.2-p12.2 microduplication syndrome","assembly":"GRCh37/hg19","remapped_from":null,"original_position":null,"grade":null,"id":92,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical: \u003c/b\u003e This 16p11.2-p12.2 duplication syndrome is a recurrent genomic condition, characterised by developmental delay, autistic and/or repetitive behaviour, dysmorphic features, microcephaly, short stature and tapering fingers (Barber \u003ci\u003eet al\u003c/i\u003e, 2013). Developmental and/or psychomotor delay was present in all patients and normal development in two instances was followed by a marked decline after the age of two. Intellectual disability varied from severe to moderate or mild and very mild in a patient with a smaller duplication that did not include the distal 16p11.2 microdeletion region (Okamoto \u003ci\u003eet al\u003c/i\u003e, 2014, Patient 2). Autistic, obsessive or stereotyped behaviour was recorded in most patients but less than half had a formal diagnosis of autism according to ADI-R or DSM IV. Other less common features included ADHD or hyperactivity, echolalia, MRI/CT scan anomalies, seizures and/or EEG anomalies.\u003c/p\u003e\u003cp\u003eDysmorphism was also found in most patients but was absent in a mildy affected mother and daughter who had the same duplication as each other (Engelen \u003ci\u003eet al\u003c/i\u003e, 2002). Common dysmorphisms included a depressed, broad or large nasal bridge, upslanting or narrow palpebral features, hypertelorism and a long or tented philtrum. Other less common physical features included short stature, microcephaly, nystagmus or strabismus, digital anomalies and skin syndactyly of the feet. The only case of a congenital heart defect resolved spontaneously. Recurrent infections were recorded in some patients.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication: \u003c/b\u003eThe minimum size of pure 16p11.2-p12.2 duplications varied from 6.71 Mb to 8.95 Mb when analysed using microarrays (Okamoto \u003c/i\u003eet al\u003c/i\u003e, 2014; Barber \u003ci\u003eet al\u003c/i\u003e, 2013; Tabet \u003ci\u003eet al\u003c/i\u003e, 2012). The smallest 6.71 Mb duplication extended from 28.23 to 21.52 Mb (hg19) (Okamoto \u003ci\u003eet al\u003c/i\u003e, 2014, Patient 2). Most of the 16p11.2-p12.2 duplications contain at least 65 coding genes of which the Polo-like kinase 1 gene (PLK1) was thought most likely to be dosage sensitive (Barber \u003ci\u003eet al\u003c/i\u003e, 2013). The 16p11.2-p12.2 duplications are also the reciprocal of the 16p11.2-p12.2 deletions described by Ballif \u003ci\u003eet al\u003c/i\u003e, 2007 and others.\u003c/p\u003e\u003cp\u003eAll the 16p11.2-p12.2 duplications include the 16p12.1 microdeletion/microduplication region and all but one (Okamoto \u003ci\u003eet al\u003c/i\u003e, 2014, Patient 2) include the distal (formerly atypical) 16p11.2 microdeletion syndrome region (Barber et al, 2013). In another instance, the common 16p11.2 microdeletion/microduplication syndrome region was also included (Tabet \u003ci\u003eet al\u003c/i\u003e, 2012). As a result, candidate genes for these syndromes may also be involved in the 16p11.2-p12.2 phenotype, for instance the cerebellar degeneration-related protein 2 gene (CDR2) implicated in the developmental or behavioural problems found in the 16p12.1 microdeletion syndrome. The second hit hypothesis in which CNVs elsewhere in the genome have an effect on the phenotypic outcome of proximal 16p CNVs may also apply (Girirajan \u003c/i\u003eet al\u003c/i\u003e, 2010).\u003c/p\u003e\u003cp\u003e\u003ci\u003ePlease note: \u003c/i\u003e the 16p11.2-p12.2 duplication cannot be reliably distinguished from the harmless euchromatic variants (EVs) of 16p11.2 using conventional cytogenetics. These EVs involve high level CNV of repeats in 16p11.2 that are proximal to the 16p11.2-p12.2 duplications and can be distinguished using FISH or microarray analysis (Barber \u003ci\u003eet al\u003c/i\u003e, 2013).\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of the duplication: \u003c/b\u003eMost cases are \u003ci\u003ede novo\u003c/i\u003e and believed to arise as a result of non-allelic homologous recombination (NAHR) between segmentally duplicated repeats in proximal 16p (Finelli \u003ci\u003eet al\u003c/i\u003e, 2004; Barber \u003ci\u003eet al\u003c/i\u003e, 2013). The size varies according to which hot spots have been involved at the distal and proximal ends of each duplication (Girirajan \u003ci\u003eet al\u003c/i\u003e, 2010).\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert Advisor: \u003c/b\u003e Dr John Barber, Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p11.2%20microduplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=261204\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","is_draft":0,"end":29284077,"syndrome_id":96,"start":21475060,"syndrome_cnv_id":92,"updated":"2015-07-06 09:39:46","genotype":"Heterozygous","created":"2013-05-09 18:53:04","chr":"16"},{"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rubinstein-taybi.org/\"\u003ewww.rubinstein-taybi.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rtsuk.org/home/index.asp\"\u003ewww.rtsuk.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2016/16p13%20deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1526/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=783\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion","remapped_from":null,"grade":1,"original_position":null,"id":22,"short_description":"Rubinstein-Taybi Syndrome","assembly":"GRCh37/hg19","remap_value":null,"chr":"16","created":"2012-07-31 12:15:00","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.93511","syndrome_cnv_id":22,"syndrome_id":7,"start":3775055,"end":3930121,"is_draft":0},{"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Girirajan \u003ci\u003eet al\u003c/i\u003e detected this microdeletion in 20 of 11,873 cases with intellectual disability/developmental delay compared with 2 of 8540 controls and in a second, replication series of 22 of 9,254 cases compared with 6 of 6,299 controls (combined 42/21,127 cases, 8/14,839 controls; P= 0.000118).  Most deletions were inherited and carrier parents were more likely to manifest neuropsychiatric phenotypes compared to non-carrier parents and this observation just achieved statistical significance (P=0.037). This microdeletion has been implicated as one of the most common contributory genetic causes of susceptibility to developmental delay associated phenotypes. Girirajan  \u003ci\u003eet al\u003c/i\u003e postulate a 2-hit model in which the 16p12.1 microdeletion predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in concert with other large (\u003e500 kbp) deletions/duplications.?\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e 520kb sponsored by two segmental duplication blocks.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e The short arm of 16p is particularly enriched for large segmental duplications that sponsor NAHR. Most deletions are inherited.\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert Advisor:\u003c/b\u003e Dr. Santhosh Girirajan, Department of Biochemistry and Molecular Biology, Pennsylvania State University, USA\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://omim.org/136570\"\u003eomim.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","remapped_from":null,"id":88,"original_position":null,"grade":null,"short_description":"Recurrent 16p12.1 microdeletion (neurodevelopmental susceptibility locus)","assembly":"GRCh37/hg19","remap_value":null,"chr":"16","created":"2013-01-31 15:43:13","genotype":"Heterozygous","updated":"2014-07-02 09:23:46.251066","syndrome_cnv_id":88,"syndrome_id":92,"start":21946524,"is_draft":0,"end":22467284}]}
{"CNV":[{"remap_value":null,"assembly":"GRCh37/hg19","short_description":"RCAD (renal cysts and diabetes)","original_position":null,"id":47,"grade":null,"remapped_from":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e RCAD encompasses a wide clinical spectrum comprising developmental kidney abnormalities (particularly renal cysts, glomerulocystic kidney disease, renal dysplasia) usually present in early life, and diabetes typically diagnosed in the early 20s and usually insulin treated and associated with pancreatic atrophy with subclinical exocrine deficiency. Mildly abnormal liver enzymes are common and some patients have hyperuricaemia and gout. Uterine or genital anomalies are described. Many cases are sporadic cases reflecting spontaneous mutations /deletions.\u003c/p\u003e\u003cp\u003eRCAD is caused by mutations of the \u003ci\u003eTCF2\u003c/i\u003e gene encoding the transcription factor hepatocyte nuclear factor 1beta. Approximately 50% of cases of RCAD result from a large deletion encompassing \u003ci\u003eTCF2\u003c/i\u003e. The phenotype of patients with point mutations and those with deletions appears to be indistinguishable.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e The common minimal deletion encompasses a genomic region of 1.2Mb.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e The breakpoints flanking the common minimal deletion are both located in repetitive sequences (a LINE-2 element and an MIR element).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Andrew Hattersley, Professor of Molecular Medicine,Peninsula Medical School, Exeter,UK\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.diabetesgenes.org/content/renal-cysts-diabetes-rcad\"\u003ewww.diabetesgenes.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2017/17q12%20microdeletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93111\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"is_draft":0,"end":36215917,"start":34815072,"syndrome_id":47,"syndrome_cnv_id":47,"updated":"2014-07-02 09:23:45.98068","genotype":"Heterozygous","created":"2012-07-31 14:56:15","chr":"17"},{"remap_value":null,"short_description":"Smith-Magenis Syndrome","assembly":"GRCh37/hg19","remapped_from":null,"grade":1,"original_position":null,"id":15,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Patients generally have flat, square, rather heavy facies. They are often short and obese with small hands & feet. They may have a history of hypotonia in infancy, developmental delay, behaviour disturbance (especially sleep disturbances and self-injurious behaviours), and sometimes food-searching behaviour. All individuals with Smith-Magenis syndrome have mild to severe learning disabilities with no differences overall between verbal and performance skills, but with a particular profile of cognitive strengths and weaknesses. Levels of attainment and of adaptive behaviour were low, and adults with Smith Magenis syndrome were more dependent on carers than might be expected from their general level of intellectual functioning.\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - In \u003e70% of patients with SMS, identical approximately 3.7 Mb deletions in 17p11.2 have been identified. These deletions are flanked by large (approximately 200 kb), highly homologous, directly oriented LCRs (i.e., proximal and distal SMS repeats [SMS-REPs]). The third (middle) SMS-REP is inverted with respect to them and maps inside the commonly deleted genomic region. ~25% have unusual smaller or larger deletions ranging in size from ~1.5 to ~9 Mb. Less than 5% of individuals with Smith Magenis syndrome have point mutations in \u003ci\u003eRAI1\u003c/i\u003e, a gene encompassed by the common 17p11.2 microdeletion.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - The common SMS deletion arises with equivalent frequency on the maternal and paternal chromosome from unequal crossing over due to homologous recombination between flanking repeat gene clusters. The reciprocal duplication of the same region causes the dup(17)(p11.2p11.2) syndrome.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e Weimin Bi, Ph.D., Department of Molecular & Human Genetics, Baylor College of Medicine, Houston,USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.smith-magenis.co.uk/\"\u003ewww.smith-magenis.co.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.prisms.org/\"\u003ewww.prisms.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1310/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=819\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","is_draft":0,"end":20222149,"syndrome_id":8,"start":16773072,"syndrome_cnv_id":15,"updated":"2014-07-02 09:23:45.936295","genotype":"Heterozygous","created":"2012-07-31 12:23:10","chr":"17"},{"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e Type 1 neurofibromatosis (NF-1) is an autosomal dominant disorder with a birth incidence of 1 in 2500 and a prevalence of 1 in 4000. The cardinal features are cafe-au-lait spots, neurofibromas and Lisch nodules in the iris. NF-1 shows hugely variable expressivity and many of the features of NF-1 show age-dependent penetrance. ~5% of NF-1 patients carry a heterozygous large deletion involving the NF-1 gene and contiguous genes. NF-1 patients with large deletions frequently show a more severe phenotype than observed in classical NF-1 patients with intragenic mutations and are more likely to have dysmorphic features, cardiac anomalies and mental retardation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e The majority (~62%) of patients with an NF1 microdeletion have a common deletion which is sponsored by unequal homologous recombination of NF1 low-copy repeats (REPs).These type I deletions are 1.4 Mb in size and encompass 14 genes. Kehrer-Sawatzki identified a second major type of NF1 microdeletion, which spans 1.2 Mb and affects 13 genes. This type II deletion was found in 8 (38%) of 21 patients and is mediated by recombination between the \u003ci\u003eSUS12 (JJAZ1)\u003c/i\u003e gene and its pseudogene. The \u003ci\u003eSUS12\u003c/i\u003e gene, which is completely deleted in patients with type I NF1 microdeletions and is disrupted in deletions of type II, is highly expressed in brain structures associated with learning and memory. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Type I NF1 microdeletions occur by interchromosomal recombination during meiosis, whereas type II deletions are mediated by intrachromosomal recombination during mitosis. A significant proportion of sporadic patients with type II deletions are somatic mosaics. A few patients have unusual sized deletions, incorporating the NF1 gene. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Hildegard Kehrer-Sawatzki, Ph.D., Department of Human Genetics, University of Ulm, Ulm, Germany\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.nfauk.org\"\u003ewww.nfauk.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ctf.org/\"\u003ewww.ctf.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1109/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=636&Lng=GB\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","id":19,"original_position":null,"grade":1,"remapped_from":null,"short_description":"NF1-microdeletion syndrome","assembly":"GRCh37/hg19","remap_value":null,"chr":"17","created":"2012-07-31 12:27:46","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.939921","syndrome_cnv_id":19,"start":29107097,"syndrome_id":15,"end":30263321,"is_draft":0},{"remap_value":null,"assembly":"GRCh37/hg19","short_description":"Hereditary Liability to Pressure Palsies (HNPP)","id":37,"original_position":null,"grade":1,"remapped_from":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - The history is of recurrent focal pressure nerve palsies (eg. carpal tunnel syndrome, and peroneal palsy with foot drop). Some patients develop pes cavus. There is usually an AD history of similar problems. Typically nerve conduction studies show prolongation of median nerve conduction latency in all patients whether symptomatic or symptom-free. General motor nerve conduction velocities are usually normal (greater than 40m/s). Some patients have electrical evidence of a mild diffuse polyneuropathy.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - The commonest molecular defect in HNPP, occurring in 80%, is a 1.5 Mb deletion at 17p11.2 arising from unequal crossing over of homologous chromosomes at regions of low copy repeats flanking the deleted region. Duplication of the same region causes Charcot Marie Tooth Disease type 1A (CMT1A). ~20% of patients have a point mutation (usually a frameshift) in PMP22\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.hnpp.org/\"\u003ewww.hnpp.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1392/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=640\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","end":15470903,"is_draft":0,"start":14097915,"syndrome_id":31,"syndrome_cnv_id":37,"updated":"2014-07-02 09:23:45.96375","genotype":"Heterozygous","created":"2012-07-31 14:11:31","chr":"17"},{"chr":"17","created":"2012-07-31 14:01:58","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.952826","syndrome_cnv_id":32,"start":1,"syndrome_id":21,"is_draft":0,"end":2588909,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Miller-Dieker syndrome is characterised by lissencephaly ('smooth brain' with lack of normal gyri and sulci) with dysmorphic features. The microdeletion includes the \u003ci\u003eLIS1\u003c/i\u003e gene. The abnormalities of gyration are a consequence of abnormal/deficient neuronal migration from the inner ventricular zone to the outer cortical plate due to deletion of the \u003ci\u003eLIS1\u003c/i\u003e gene. Patients with MDS have larger and more telomeric deletions than those with isolated lissencephaly sequence. and the deletions always include the gene encoding 14-3-3epsilon(Toyo-oka). In about 12% the deletion is due to a familial chromosome rearrangement. \u003c/p\u003e\u003cp\u003eThe main dysmorphic features are: tall prominent forehead with vertical furrowing, bitemporal narrowing, hypertelorism, upslanting palpebral fissures, short nose with anteverted nares, inverted vermilion border of upper lip with long, broad and thick upper lip. There are associated anomalies, like congenital heart disease, omphalocele and joint contractures.Patients with MDS usually have severe mental handicap, epilepsy and a reduced lifespan.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Variable, from 0.1Mb-2.9Mb\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e William B. Dobyns, MD, University of Chicago, Dept. Human Genetics, Chicago, Illinois, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://ghr.nlm.nih.gov/condition/miller-dieker-syndrome\"\u003eghr.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=531\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","original_position":null,"id":32,"grade":1,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"Miller-Dieker syndrome (MDS)","remap_value":null},{"chr":"17","created":"2012-07-31 13:53:13","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.949043","syndrome_cnv_id":24,"start":16773072,"syndrome_id":19,"end":20222149,"is_draft":0,"copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - The phenotype is generally mild with normal facies, mild mental retardation/borderline normal cognitive function and behavioural difficulties. Attention deficit disorder and hyperactivity are common and some have autistic features. Most have short stature; in Potocki's series 5/7 patients were >5th centile for height.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication\u003c/b\u003e - The size of the duplication is identical to the deletion seen in Smith Magenis syndrome ie. approximately 3.7-Mb. The duplication is flanked by large (approximately 200 kb), highly homologous, directly oriented LCRs (i.e., proximal and distal SMS repeats [SMS-REPs]). \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication\u003c/b\u003e - In Potocki's series 5/7 arose on the paternal chromosome. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003eLorraine Potocki, Associate Professor, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.potockilupskisyndrome.org/\"\u003ewww.potockilupskisyndrome.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2017/Duplications%20of%2017p%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.bcm.edu/genetics/potocki_lupski/\"\u003ewww.bcm.edu\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to futher information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=1713&Lng=GB\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","variant_class":"Duplication","original_position":null,"id":24,"grade":null,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"Potocki-Lupski syndrome (17p11.2 duplication syndrome)","remap_value":null},{"short_description":"17q21.31 recurrent microdeletion syndrome (Koolen de Vries syndrome)","assembly":"GRCh37/hg19","remap_value":null,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e The syndrome is very variable, but common features include: low birthweight (0.4th-9th centile), neonatal hypotonia, poor feeding in infancy (often requiring naso-gastric feeding for a period) and oromotor dyspraxia together with moderate developmental delay/learning disability but friendly/amiable behaviour. Other clincially important features include epilepsy, heart defects (ASD, VSD) and kidney/urological anomalies. Silvery depigmentation of strands of hair have been noted in several patients. With age there is an apparent coarsening of facial features. 17q21.3 was reported simultaneously in 2006 by three independent groups. A reciprocal microduplication of 17q21.3 had also been described (Kirchhoff 2007). Koolen (2008) provides an overview of the clinical features of the syndrome by reviewing 22 individuals with a 17q21.3 microdeletion and estimate a prevalence of ~1/16,000. Koolen (2012) and Zollino (2012) recently showed that haploinsufficiency of the gene KANSL1, a regulator of chromosome modification, is sufficient to cause the 17q21.31 microdeletion syndrome.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e The recurrent deletion is between 500-650kb in size encompassing the KAT8 regulatory NSL complex subunit 1 (\u003ci\u003eKANSL1\u003c/i\u003e) gene.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e A 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. The orientation of LCRs flanking the deleted segment in inversion heterozygotes, or H2 homozygotes, sponsors this microdeletion by means of non-allelic homologous recombination (NAHR) and Koolen (2008) showed that in the 5 cases examined, the parent originating the deltion carried the common 900kb 17q21.31 inversion polymorphism (H2 haplotype) p>10-5.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Helen V Firth, Consultant Clinical Geneticist, Addenbrooke's Hospital, Cambridge, UK\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2017/17q21.31%20microdeletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://17q21.com\"\u003e17q21.com\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=96169\"\u003ewww.orpha.net\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/10727/17q2131-microdeletion-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","variant_class":"Deletion","remapped_from":null,"grade":1,"original_position":null,"id":55,"updated":"2014-07-02 09:23:45.997275","syndrome_cnv_id":55,"syndrome_id":57,"start":43705166,"end":44294406,"is_draft":0,"chr":"17","created":"2012-08-10 12:23:00","genotype":"Heterozygous"},{"genotype":"Heterozygous","created":"2012-07-31 14:09:30","chr":"17","end":15470903,"is_draft":0,"start":14097915,"syndrome_id":29,"syndrome_cnv_id":36,"updated":"2014-07-02 09:23:45.961576","original_position":null,"grade":1,"id":36,"remapped_from":null,"variant_class":"Duplication","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - CMT1A is a demyleinating peripheral neuropathy characterised by distal muscle weakness and atrophy associated with mild/moderate glove & stocking sensory loss, depressed reflexes and pes cavus. CMT1A follows an autosomal dominant pattern of inheritance with age-dependent penetrance and variable expressivity. It usually presents between the ages of 5-15 years with difficulty walking due to problems picking up the feet ('foot drop'). Gradual loss of muscle bulk in the lower calves leads to weakness wth dosiflexion and eversion of the foot. Weakness of the hands may occur later and is rarely symptomatic before adult life. The weakness is very slowly progressive. Affected individuals may also have a loss of sensation in the hands and feet.\u003c/p\u003e\u003cp\u003eSometimes CMT1A presents considerably later, even into middle age and a small percentage (~10%) of individuals remain largely asymptomatic in adult life, but with changes detectable on careful clinical assessment and/or nerve conduction studies.\r\u003c/p\u003e\u003cp\u003eThe CMT1A duplication incorporates the PMP22 gene. Peripheral myelin protein 22 is a major component of myelin expressed in the compact portion of essentially all myelinated fibers in the peripheral nervous system and is produced predominantly by Schwann cells. In CMT1A, nerve conduction velocities (NCV's) are slow, typically 10-30 m/s.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication\u003c/b\u003e - The 1.5 Mb duplication at 17p11.2, which defines CMT1A is a recurrent duplication flanked by low copy repeats. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication\u003c/b\u003e - The duplication arises from unequal crossing over of homologous chromosomes at regions of low copy repeats flanking the duplicated region. Deletion of the same region causes the milder phenotype Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). In ~2/3rds of individuals the duplication is inherited; it arises \u003ci\u003ede novo\u003c/i\u003e in the remaining 1/3rd. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.cmt.org.uk/\"\u003ewww.cmt.org.uk\u003c/a\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2017/Duplications%20of%2017p%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=101081\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":3,"remap_value":null,"short_description":"Charcot-Marie-Tooth syndrome type 1A (CMT1A)","assembly":"GRCh37/hg19"}]}
{"CNV":[{"grade":null,"original_position":null,"id":48,"remapped_from":null,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Early onset progressive dementia of Alzheimer disease type with a mean age of onset of 52 years (Rovelet-Lecrux) due to duplication of the APP locus. Neuropathological features included neurofibrillary tangles and cerebral amyloid angiopathy. These neuropathological findings are also typical of the early-onset Alzheimer disease seen in patients with Down syndrome (Trisomy 21) who also have three copies of the APP locus (which is located on proximal 21q).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e Variable. In the original paper by Rovelet-Lecrux, the duplication size varied from 0.58-6.37Mb including a minimum critical interval incorporating the APP gene of 0.58Mb. In a cohort of patients with autosomal dominant early-onset Alzheimer disease, the frequency of APP locus duplication was ~8%. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003eUnknown\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Dominique Campion, Inserm U614-IFRMP, Faculty of Medicine, Rouen, France.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://alzheimers.org.uk\"\u003ealzheimers.org.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1236/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1020\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":3,"variant_class":"Duplication","remap_value":null,"assembly":"GRCh37/hg19","short_description":"Early-onset Alzheimer disease with cerebral amyloid angiopathy","created":"2012-07-31 14:59:16","genotype":"Heterozygous","chr":"21","start":27252860,"syndrome_id":48,"end":27543446,"is_draft":0,"updated":"2014-07-02 09:23:45.981971","syndrome_cnv_id":48}]}
{"CNV":[{"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e All 6 patients descrived in the paper by Ben-Shachar have dysmorphic facial features. Prematurity, prenatal and postnatal growth delay, developmental delay, and mild skeletal abnormalities are common features. 2/6 patients have a cardiovascular malformation, (truncus arteriosus in one, and bicuspid aortic valve in the other). A single patient had a cleft palate.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e The recurrent deletions are either approximately 1.4 Mb or approximately 2.1 Mb ins size with a common proximal breakpoint flanked by LCR22-4. They differ at the distal breakpoints flanked by either LCR22-5 for the smaller deletion or LCR22-6 for the larger deletion.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e In the paper by Ben-Shachar et al in all of the trios tested (5), the deletion was \u003ci\u003ede novo\u003c/i\u003e in origin.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Shay Ben-Shachar, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2022/22q11.2%20deletions%20syndrome%20%28Velo-Cardio-Facial%20Syndrome%29%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=261330\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","grade":null,"original_position":null,"id":71,"remapped_from":null,"short_description":"22q11.2 distal deletion syndrome","assembly":"GRCh37/hg19","remap_value":null,"chr":"22","genotype":"Heterozygous","created":"2012-08-01 11:55:46","syndrome_cnv_id":71,"updated":"2014-07-02 09:23:46.230987","end":23722445,"is_draft":0,"start":21917117,"syndrome_id":72},{"syndrome_cnv_id":21,"updated":"2014-07-02 09:23:45.941828","is_draft":0,"end":21452445,"syndrome_id":16,"start":19009792,"chr":"22","genotype":"Heterozygous","created":"2012-07-31 12:37:48","assembly":"GRCh37/hg19","short_description":"22q11 deletion syndrome (Velocardiofacial / DiGeorge syndrome)","remap_value":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Most patients with a hemizygous deletion of 22q11.2, have outflow tract heart defects, immune deficiency, transient neonatal hypocalcemia, velopharyngeal insufficiency and a distinctive facial appearance. Most also have learning disabilities and behavioral anomalies including schizophrenia in some adult patients. A small subset have a missing thymus gland and severe neonatal hypocalcemia (DiGeorge sequence). Most of the defects result from abnormal development of the pharyngeal apparatus. Haploinsufficiency of TBX1, a T-gene transcription factor or mutation (Yagi), appears to be a major contributor to the phenotype. Another gene, CRKL, also mapping to 22q11.2 is likely a modifier of the syndrome (Guris). \u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Microdeletions of 22q11.2 usually encompass ~3Mb of genomic DNA and are detectable by FISH analysis. There are several low-copy repeats on chromosome 22 (LCR22). Those flanking the 22q11 deletion region appear to facilitate homologous recombination; however misalignment between blocks of LCR22's is likely to facilitate the deletion. Most VCFS/DGS patients have a 3Mb deletion, some have a nested distal deletion breakpoint resulting in a 1.5Mb deletion and a few rare patients have unique deletions, translocations or point mutations of TBX1 (Yagi). Overall ~96% of patients have a defined 1.5-3Mb deletion including 24-30 genes.\r\u003c/p\u003e\u003cp\u003e \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - In approximately 94% the deletion is 'de novo', with 6% being inherited from a parent. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e Dr Bernice Morrow, Professor of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.maxappeal.org.uk\"\u003ewww.maxappeal.org.uk\u003c/a\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.vcfsef.org\"\u003ewww.vcfsef.org\u003c/a\u003e \r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.22q.org/\"\u003ewww.22q.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1523/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=567&Lng=GB\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","remapped_from":null,"grade":1,"original_position":null,"id":21},{"is_draft":0,"end":21452445,"syndrome_id":32,"start":19009792,"syndrome_cnv_id":38,"updated":"2014-07-02 09:23:45.965118","genotype":"Heterozygous","created":"2012-07-31 14:13:21","chr":"22","remap_value":null,"short_description":"22q11 duplication syndrome","assembly":"GRCh37/hg19","remapped_from":null,"original_position":null,"id":38,"grade":3,"variant_class":"Duplication","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - 22q11 duplication syndrome is not a clinically recognizable disorder; it is diagnosed following molecular genetic analysis revealing a duplication of 22q11.2\u003c/p\u003e\u003cp\u003eThe most frequent reported symptoms in probands with duplication of 22q11.2 duplication syndrome are mental retardation/learning disabilility (97%), delayed psychomotor development (67%), growth retardation (63%) and muscular hypotonia (43%) [Wentzel 2008]. However, these are common and relatively non-specific indications for cytogenetic analysis, and the extent to which duplication of 22q11.2 is causal for these features is currently unknown.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication\u003c/b\u003e - Duplications of 22q11 vary in size and thereby in gene content. They include the typical common 3-Mb microduplication, 1.5-Mb nested duplication, consistent with nonallelic homologous recombination (NAHR) using distinct low-copy repeats (LCR 22???????¬?????s). These microduplications likely represent the predicted reciprocal rearrangements to the microdeletions characterized in the 22q11.2 region [Ou 2008]. Smaller microduplications may occur within this highly dynamic with frequent rearrangements using alternative low-copy repeats (LCR-22???????¬?????s) as recombination substrates within and distal to the DiGeorge/velocardiofacial syndrome region.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication\u003c/b\u003e - The majority of 22q11 duplications are inherited often from a parent with a normal/near-normal phenotype. This is in sharp distinction to 22q11 deletion syndrome where ~90% of cases occur \u003ci\u003ede novo\u003c/i\u003e. This observation implies a strongly differential effect of copy number of this interval on reproductive fitness.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003eProf. Heather McDermid, Department of Biological Sciences, University of Alberta, Edmonton, Canada \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.c22c.org/22q11dup.htm\"\u003ewww.c22c.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2022/22q11.2%20duplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK3823/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1727\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":3},{"chr":"22","created":"2008-06-07 12:45:59","genotype":"Heterozygous","updated":"2014-07-02 09:23:45.950914","syndrome_cnv_id":30,"start":51045516,"syndrome_id":20,"is_draft":0,"end":51187844,"copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - All individuals reported have severe expressive language delay, behavioural disturbance (hyperactivity, aggressive outbursts) and hypotonia. The facial dysmorphic features are subtle and variable. Overgrowth has been reported. Hypotonia, usually acquired rather than neonatal is a common feature, present in \u003e80% in Luciani's series. Severe expressive speech delay is a constant feature. Behavioural disorders are generally present in children \u003e1yr eg. hyperactivity, sleep disturbance. \u003ci\u003eSHANK3\u003c/i\u003e (also known as \u003ci\u003eProSAP2\u003c/i\u003e) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Durand et al recently showed that mutation of a single copy of \u003ci\u003eSHANK3\u003c/i\u003e on chromosome 22q13 can result in language and/or social communication disorders. >This observation explains why 22q13 deletion syndrome, which includes haploinsufficiency for \u003ci\u003eSHANK3\u003c/i\u003e, is characterised by a severe linguistic and/or social communication disorder. No apparent life-threatening organic abnormalities accompany the diagnosis of deletion 22q13 (Phelan).\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Deletions are extremely variable in size from 160kB to 9Mb in the series reported by Luciani. The minimal critical region, associated with a phenotype of mild global developmental delay and severe language impairment is distal to the ARSA probe that is used as a 22q control for del (22q11.2). Wilson compared clinical features to deletion size and showed few correlations. Some measures of developmental assessment did correlate to deletion size; however, all patients showed some degree of mental retardation and severe delay or absence of expressive speech, regardless of deletion size. Similarly, Koolen in a study of 9 patients with deletions varying between 3.3-8.4Mb found that global developmental delay and absent or severely delayed speech were observed in all patients, with hypotonia present in 8/9. Bonaglia et al (2005) identified a common breapoint within a 15bp repeat unit in the SHANK3 gene in 2 patients, identical to that previously reported by Wong et al in 1997. The 3 patients showed mental retardation and developmental delay with severely delayed or absent expressive speech reinforcing the observation that the main phenotypic determinants of 22q13 syndrome lie in the terminal 100kb of 22q.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Luciani found a strong excess of paternal origin for all classes of rearrangement\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e - Prof. Orsetta Zuffardi, Genetica Medica, Universit????  di Pavia, Pavia, Italy\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.22q13.org/\"\u003ewww.22q13.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome%2022/22q13%20deletions%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1198/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=48652\"\u003ewww.orpha.net\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","variant_class":"Deletion","grade":1,"original_position":null,"id":30,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"22q13 deletion syndrome (Phelan-Mcdermid syndrome)","remap_value":null},{"chr":"22","genotype":"Homozygous","created":"2007-04-12 12:36:12","syndrome_cnv_id":42,"updated":"2014-07-02 09:23:45.973345","is_draft":0,"end":16971860,"start":1,"syndrome_id":42,"variant_class":"Duplication","copy_number":4,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Phenotypes range from mild to severe, and can vary considerably within and between families. The syndrome takes its name from ocular coloboma, which is present in 55-60% of cases (Berends, Rosias). Other typical features include preauricular skin tags and pits, anal anomalies (such as anal atresia), cardiovascular defects (especially septal defects and the relatively rare total anomalous pulmonary venous return/drainage/connection), other ocular defects, urogenital malformations, skeletal defects, and abdominal malformations. Common dysmorphic features include downslanting palpebral fissures, hypertelorism, low set or dysplastic ears, epicanthal folds, strabismus, and micrognathia. Varying degrees of mental retardation is seen, although as many as 47% of cases fall within the normal range (over IQ of 85) (Berends). \u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e CES is usually associated with a supernumerary bisatellited dicentric marker chromosome of chromosome 22 origin. This dicentric chromosome is usually stable, although a proportion of cases show mosaicism. The CES marker includes two copies of the 22 p-arm, although this is thought to have no phenotypic consequences. Because the chromosome originates from two chromosomes 22, there are two 22q11 breakpoints, which are thought to occur in the low copy repeats (LCRs) that flank the DiGeorge syndrome/velocardiofacial syndrome (DGS/VCFS) deletion region. Thus all CES markers contain two copies of the 22q11 CES region, adjacent to the centromere. Type I CES markers have both breakpoints at the proximal LCR, and therefore do not contain the DGS/VCFS region. Type II CES markers have one or both breakpoints at the distal LCR, and therefore contain one or two copies of the DGS/VCFS region in addition to two copies of the CES region.\r\u003c/p\u003e\u003cp\u003eCES has also been seen in patients with interstitial duplication of 22q11. To date these cases have included most of the CES region and the DGS/VCFS region, as well as varying degrees of more distal regions. This indicates that three copies of these regions of 22q11 are sufficient to cause the syndrome.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e Both de novo and familial cases have been reported. The marker chromosome is sometimes mosaic. \r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Prof. Heather McDermid, Department of Biological Sciences, University of Alberta, Edmonton, Canada. Reviewed August 2005\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.c22c.org/ces.htm\"\u003ewww.c22c.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=195\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/26/cat-eye-syndrome/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","id":42,"original_position":null,"grade":null,"remapped_from":null,"assembly":"GRCh37/hg19","short_description":"Cat-Eye Syndrome (Type I)","remap_value":null}]}
{"CNV":[{"remap_value":null,"assembly":"GRCh37/hg19","short_description":"Leri-Weill dyschondrostosis (LWD) - SHOX deletion","id":56,"original_position":null,"grade":null,"remapped_from":null,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Leri-Weill dyschondrostsosis (LWD) is a pseudoautosomal dominant disorder characterised by short stature, mesomelic limb shortening and a characteristic 'Madelung' deformity of the forearms (bowing of the radius and restriction of pronation/supination of the forearm). It is caused by deletions of the SHOX gene, point mutations in the SHOX gene or deletions centromeric to the gene which presumably interfere with regulatory elements. The phenotype in LWD is very variable, and in some patients the only discernible phenotype is short stature.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e SHOX deletions vary widely in size, from ~10kb to ~1Mb. Some deletions encompass the SHOX gene, whereas others are centromeric to SHOX within psuedoautosomal region (PAR1).There is no discernible phenotypic difference between those with a deletion of SHOX and those with PAR1 deletions located downstream of SHOX. Amongst the latter group, there is a common ~10.5kb interval ~200kb centromeric to SHOX which presumably contains a critical regulatory element for the SHOX gene. There is no common recurrent deletion, but for deletions encompassing SHOX there appears to be a common proximal breakpoint in the majority (73%)of patients (Schneider). \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e Deletions may be inherited or arise 'de novo'. In a large French series (Huber), of 8 'de novo' deletions, all arose on the paternal allele, perhaps due to the high rate of recombination between sex chromosomes during male meiosis, which is restriced to the pseudoautosomal regions (PAR).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Valerie Cormier-Daire, Dept of Medical Genetics and INSERM U781, Hopital Necker Enfants Malades, Paris, France.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e \r\u003c/p\u003e\u003cp\u003eChild Growth Foundation \u003ca href=\"http://childgrowthfoundation.org\"\u003echildgrowthfoundation.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=240.0\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/3224/leri-weill-dyschondrosteosis/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":1,"variant_class":"Deletion","start":751878,"syndrome_id":58,"end":867875,"is_draft":0,"updated":"2014-07-02 09:23:46.000482","syndrome_cnv_id":56,"created":"2006-09-14 15:02:37","genotype":"Heterozygous","chr":"X"},{"remap_value":null,"short_description":"Xp11.22-p11.23 Microduplication","assembly":"GRCh37/hg19","original_position":null,"id":85,"grade":null,"remapped_from":null,"variant_class":"Duplication","description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Data Awaited\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome_X/Xp11.2%20duplications%20FTNP.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=217377\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://omim.org/entry/300801\"\u003eomim.org\u003c/a\u003e\u003c/p\u003e","copy_number":3,"end":52117661,"is_draft":0,"start":48334549,"syndrome_id":89,"syndrome_cnv_id":85,"updated":"2014-07-02 09:23:46.247662","genotype":"Unknown","created":"2012-08-13 10:42:24","chr":"X"},{"start":103031438,"syndrome_id":38,"end":103047547,"is_draft":0,"updated":"2014-07-02 09:23:45.97065","syndrome_cnv_id":51,"created":"2012-07-31 14:26:39","genotype":"Unknown","chr":"X","remap_value":null,"assembly":"GRCh37/hg19","short_description":"Pelizaeus-Merzbacher disease","id":51,"original_position":null,"grade":null,"remapped_from":null,"copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Pelizaeus-Merzbacher disease (PMD) typically onsets in infancy or early childhood with nystagmus, hypotonia, and developmental delay (especially in motor function) ; the findings progress to severe spasticity, ataxia and choreoathetotic movement. Because PMD essentially result in a failure to produce myelin (dysmyelination) in the central nervous system, children with PMD have a diffuse leukoencephalopathy and cranial T2-enhanced MRI scans show diffusely increased signal intensity in the central white matter of the cerebral hemispheres, cerebellum, and brainstem. The white matter is often reduced in volume, with thinness of the corpus callosum or general dealy in myelination. PMD is a life-limiting disorder. Genomic duplications involving PLP1 gene have been shown to be the principle cause of the disorder, accounting for ~50-70% of cases. PLP1 deletions are also present, but they are extremely rare.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication\u003c/b\u003e - Both duplication and deletion vary in length. Duplications range from 100Kb to \u003e7Mb, but most commonly span ~600-700 Kb. Deletions are usually less than 600 Kb.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication\u003c/b\u003e - The majority of duplications appear to originate from male meiosis by sister chromatid exchange, but the exact molecular mechanism is still unknown.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e Ken Inoue, Head, Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience National Center of Neurology and Psychiatry,\r\u003c/p\u003e\u003cp\u003e4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502 JAPAN\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarediseases.org/rare-disease-information/organizations/byID/2624/viewDetail\"\u003ewww.rarediseases.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1182/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=702\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/4265/pelizaeus-merzbacher-disease/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\u003c/p\u003e","variant_class":"Duplication"},{"remapped_from":null,"original_position":null,"id":84,"grade":null,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Data Awaited\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=293939\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","remap_value":null,"assembly":"GRCh37/hg19","short_description":"Xq28 Microduplication","genotype":"Unknown","created":"2012-08-13 10:28:07","chr":"X","end":153881853,"is_draft":0,"syndrome_id":88,"start":153624563,"syndrome_cnv_id":84,"updated":"2014-07-02 09:23:46.246731"},{"short_description":"Leri-Weill dyschondrostosis (LWD) - SHOX deletion","assembly":"GRCh37/hg19","remap_value":null,"variant_class":"Deletion","copy_number":1,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Leri-Weill dyschondrostsosis (LWD) is a pseudoautosomal dominant disorder characterised by short stature, mesomelic limb shortening and a characteristic 'Madelung' deformity of the forearms (bowing of the radius and restriction of pronation/supination of the forearm). It is caused by deletions of the SHOX gene, point mutations in the SHOX gene or deletions centromeric to the gene which presumably interfere with regulatory elements. The phenotype in LWD is very variable, and in some patients the only discernible phenotype is short stature.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion:\u003c/b\u003e SHOX deletions vary widely in size, from ~10kb to ~1Mb. Some deletions encompass the SHOX gene, whereas others are centromeric to SHOX within psuedoautosomal region (PAR1).There is no discernible phenotypic difference between those with a deletion of SHOX and those with PAR1 deletions located downstream of SHOX. Amongst the latter group, there is a common ~10.5kb interval ~200kb centromeric to SHOX which presumably contains a critical regulatory element for the SHOX gene. There is no common recurrent deletion, but for deletions encompassing SHOX there appears to be a common proximal breakpoint in the majority (73%)of patients (Schneider). \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion:\u003c/b\u003e Deletions may be inherited or arise 'de novo'. In a large French series (Huber), of 8 'de novo' deletions, all arose on the paternal allele, perhaps due to the high rate of recombination between sex chromosomes during male meiosis, which is restriced to the pseudoautosomal regions (PAR).\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert advisor:\u003c/b\u003e Dr Valerie Cormier-Daire, Dept of Medical Genetics and INSERM U781, Hopital Necker Enfants Malades, Paris, France.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e \r\u003c/p\u003e\u003cp\u003eChild Growth Foundation \u003ca href=\"http://childgrowthfoundation.org\"\u003echildgrowthfoundation.org\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=240.0\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://rarediseases.info.nih.gov/gard/3224/leri-weill-dyschondrosteosis/resources/1\"\u003erarediseases.info.nih.gov\u003c/a\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","original_position":null,"grade":null,"id":58,"remapped_from":null,"syndrome_cnv_id":58,"updated":"2014-07-02 09:23:46.000482","end":753877,"is_draft":0,"start":460558,"syndrome_id":58,"chr":"X","genotype":"Heterozygous","created":"2006-09-14 15:02:37"},{"assembly":"GRCh37/hg19","short_description":"Xp11.22-linked intellectual disability","remap_value":null,"copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Data Awaited\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.geneclinics.org/lab/mim/300705\"\u003ewww.geneclinics.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://omim.org/entry/300705\"\u003eomim.org\u003c/a\u003e\u003c/p\u003e","variant_class":"Duplication","remapped_from":null,"original_position":null,"grade":null,"id":86,"updated":"2014-07-02 09:23:46.248471","syndrome_cnv_id":86,"syndrome_id":90,"start":53401070,"is_draft":0,"end":53683275,"chr":"X","created":"2012-08-13 13:32:27","genotype":"Unknown"},{"remap_value":null,"short_description":"Xq28 (MECP2) duplication","assembly":"GRCh37/hg19","remapped_from":null,"original_position":null,"id":45,"grade":null,"variant_class":"Duplication","copy_number":3,"description":"\u003cp\u003e\u003cb\u003eClinical:\u003c/b\u003e Severe mental retardation, severe hypotonia with onset at birth and in the majority of patients a progressive lower-limb spasticity. Absent or very limited speech. Seizures are common as are recurrent severe infections. Growth parameters (including OFC) fall within the normal range. Carrier females showed complete skewing of X-inactivation. By analysis of patients with duplications in this region, Van Esch concluded that increased gene dosage of MECP2 was the most likely explanation for the severe MR phenotype present.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of duplication:\u003c/b\u003e Van Esch found variable duplication size, between 0.4-0.8Mb including the LICAM and MECP2 genes, but no consistent centromeric or telomeric breakpoint.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of duplication:\u003c/b\u003e Not known.\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003eDr Hilde Van Esch, Centre for Human genetics, University Hosptial Gasthuisberg, Leuven, Belgium\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.rarechromo.org/information/Chromosome_X/Xq28%20duplications%20FTNW.pdf\"\u003ewww.rarechromo.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK1284/\"\u003ewww.ncbi.nlm.nih.gov\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1762\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","end":153363188,"is_draft":0,"syndrome_id":45,"start":153287263,"syndrome_cnv_id":45,"updated":"2014-07-02 09:23:45.977269","genotype":"Unknown","created":"2012-08-13 10:26:02","chr":"X"},{"remap_value":null,"assembly":"GRCh37/hg19","short_description":"Steroid sulphatase deficiency (STS)","remapped_from":null,"id":35,"original_position":null,"grade":null,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - STS-deficiency or X-linked ichthyosis (XLI) affects 1/1300 - 1/1500 males. Affected males have generalized scaling that usually begins soon after birth. There may be associated corneal opacities that do not affect vision, and there is an increased incidence of cryptorchidism. \u003c/p\u003e\u003cp\u003eIn 85% - 90% of cases it is caused by a deletion which encompasses the STS gene. In perhaps 5% of cases the deletion is extensive enough to involve adjacent loci and may be cytogenetically visible. This can include an adjacent MRX gene giving rise to learning disability, with autistic spectrum problems and epilepsy in some (Gohlke). Around 10% of patients have point mutations or other intragenic mutations. Valdes-Flores demonstrated by FISH analysis that most apparently 'sporadic' affected males are due to inherited deletions; 10/12 mothers of apparently sporadic males were carriers in their series. Perinatal risks in pregnancies affected by XLI include: (i)Failure to initiate labour with prolonged gestation (postmaturity) & small increased risk of IUD and (ii)Failure to progress in labour.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - Typically 1.5Mb. Larger deletions may be associated with mental retardation as part of a contiguous gene syndrome.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - The recurrent microdeletion at Xp22.32 is due to non-allelic homologous recombination (NAHR) between the CRI-S232 low-copy repeat regions flanking the STS gene.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e John R.W. Yates, Professor of Medical Genetics and Honorary Consultant Department of Medical Genetics, Addenbrooke's Hospital, Cambridge\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.ichthyosis.co.uk/\"\u003ewww.ichthyosis.co.uk\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information:\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.geneclinics.org/lab/disease/ichthyosis%2C%20X-Linked?db=genetests&search_param=exact_match\"\u003ewww.geneclinics.org\u003c/a\u003e\u003c/p\u003e\u003cp\u003e\u003ca href=\"http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=461\"\u003ewww.orpha.net\u003c/a\u003e\u003c/p\u003e","copy_number":0,"is_draft":0,"end":8133195,"syndrome_id":27,"start":6455812,"syndrome_cnv_id":35,"updated":"2014-07-02 09:23:45.960174","genotype":"Hemizygous","created":"2012-07-31 14:07:19","chr":"X"}]}
{"CNV":[{"assembly":"GRCh37/hg19","short_description":"AZFa","remap_value":null,"copy_number":0,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Male infertility, characterised by azoospermia/severe oligospermia. AZFa contains two genes whose absence or mutation causes spermatogenic failure, \u003ci\u003eUSP9Y,\u003c/i\u003e and \u003ci\u003eDB9\u003c/i\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - 800kb\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Most AZFa deletions arise from recombination between two 10kb direct repeats that are ~800kb apart on Yq11\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","variant_class":"Deletion","remapped_from":null,"original_position":null,"id":26,"grade":null,"updated":"2014-07-02 09:23:45.954316","syndrome_cnv_id":26,"syndrome_id":23,"start":14352761,"end":15154862,"is_draft":0,"chr":"Y","created":"2005-07-29 14:34:27","genotype":"Hemizygous"},{"chr":"Y","created":"2005-07-29 18:41:02","genotype":"Hemizygous","updated":"2014-07-02 09:23:45.955952","syndrome_cnv_id":27,"syndrome_id":24,"start":24977425,"end":28033929,"is_draft":0,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Male infertility, characterised by azoospermia/severe oligospermia. The AZFc deletion consists almost entirely of very long repeat units as well as a number of testis specific genes eg. \u003ci\u003eDAZ\u003c/i\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - 3.5 Mb. \r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e - Two 229kb direct repeats flank the AZfc deletion and are thought to sponsor this deletion.\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":0,"variant_class":"Deletion","remapped_from":null,"grade":null,"original_position":null,"id":27,"short_description":"AZFc","assembly":"GRCh37/hg19","remap_value":null},{"assembly":"GRCh37/hg19","short_description":"AZFb","remap_value":null,"variant_class":"Deletion","copy_number":0,"description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e - Male infertility characterised by azoospermia.severe oligospermia. Only the proximal part of the AZFb deletion consists of large repeated sequences, the rest is single copy sequence. The common deletion includes at least 5 single copy genes and two duplicated genes.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e - 3.2 Mb\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","remapped_from":null,"original_position":null,"id":33,"grade":null,"syndrome_cnv_id":33,"updated":"2014-07-02 09:23:45.957706","is_draft":0,"end":26065197,"syndrome_id":25,"start":20118045,"chr":"Y","genotype":"Hemizygous","created":"2005-07-29 18:40:22"},{"chr":"Y","genotype":"Hemizygous","created":"2005-07-29 18:40:44","syndrome_cnv_id":29,"updated":"2014-07-02 09:23:45.959034","end":27793830,"is_draft":0,"syndrome_id":26,"start":19964826,"variant_class":"Deletion","description":"\u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e Male infertility, characterised by azoospermia/severe oligospermia.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSize of deletion\u003c/b\u003e ~6.7Mb encompassing the AZFb and AZFc deletions\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eOrigin of deletion\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eExpert adviser:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\r\u003c/p\u003e\u003cp\u003e\u003cb\u003eLinks to further information and support groups:\u003c/b\u003e\r\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","copy_number":0,"remapped_from":null,"original_position":null,"id":29,"grade":null,"short_description":"AZFb+AZFc","assembly":"GRCh37/hg19","remap_value":null}]}

Legend