BACKGROUND: Mental retardation can be caused by copy number variations (deletions, insertions, duplications), ranging in size from 1 kb to several megabases. Array based comparative genomic hybridisation (array-CGH) allows detection of an increasing number of genomic alterations. METHODS: A series of 46 patients with mental retardation and congenital abnormalities (previously screened for subtelomeric rearrangements) were evaluated for cryptic chromosomal imbalances by array-CGH. This array contains 6465 large-insert BAC/PAC clones, representing sequences uniformly distributed throughout the human genome. The results were confirmed by alternative techniques. RESULTS: Four pathogenic rearrangements were detected: two of them were novel, a deletion at 2q31.2 and a duplication at 8q12 band; the other two have been previously reported--a duplication of the Williams-Beuren region and a deletion of 3q29. By adding the subtelomeric alterations previously identified, a total rate of 18% of pathogenic rearrangements was found in the series. CONCLUSION: Based on our results, ZNF533 is the only gene contained in the overlapping region with other deletions at 2q31.2, and it is most probably the fourth zinc-finger gene implied in mental retardation. On the other hand, we propose that the CHD7 gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.
BACKGROUND:Mental retardation can be caused by copy number variations (deletions, insertions, duplications), ranging in size from 1 kb to several megabases. Array based comparative genomic hybridisation (array-CGH) allows detection of an increasing number of genomic alterations. METHODS: A series of 46 patients with mental retardation and congenital abnormalities (previously screened for subtelomeric rearrangements) were evaluated for cryptic chromosomal imbalances by array-CGH. This array contains 6465 large-insert BAC/PAC clones, representing sequences uniformly distributed throughout the human genome. The results were confirmed by alternative techniques. RESULTS: Four pathogenic rearrangements were detected: two of them were novel, a deletion at 2q31.2 and a duplication at 8q12 band; the other two have been previously reported--a duplication of the Williams-Beuren region and a deletion of 3q29. By adding the subtelomeric alterations previously identified, a total rate of 18% of pathogenic rearrangements was found in the series. CONCLUSION: Based on our results, ZNF533 is the only gene contained in the overlapping region with other deletions at 2q31.2, and it is most probably the fourth zinc-finger gene implied in mental retardation. On the other hand, we propose that the CHD7 gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.
Authors: Marjolein H Willemsen; Bridget A Fernandez; Carlos A Bacino; Erica Gerkes; Arjan P M de Brouwer; Rolph Pfundt; Birgit Sikkema-Raddatz; Stephen W Scherer; Christian R Marshall; Lorraine Potocki; Hans van Bokhoven; Tjitske Kleefstra Journal: Eur J Hum Genet Date: 2009-11-18 Impact factor: 4.246
Authors: Hagit N Baris; Wai-Man Chan; Caroline Andrews; Doron M Behar; Diana J Donovan; Cynthia C Morton; Judith Ranells; Tuya Pal; Azra H Ligon; Elizabeth C Engle Journal: Clin Case Rep Date: 2013-10-01
Authors: E Maestrini; A T Pagnamenta; J A Lamb; E Bacchelli; N H Sykes; I Sousa; C Toma; G Barnby; H Butler; L Winchester; T S Scerri; F Minopoli; J Reichert; G Cai; J D Buxbaum; O Korvatska; G D Schellenberg; G Dawson; A de Bildt; R B Minderaa; E J Mulder; A P Morris; A J Bailey; A P Monaco Journal: Mol Psychiatry Date: 2009-04-28 Impact factor: 15.992
Authors: Elisa Pisaneschi; Pietro Sirleto; Francesca Romana Lepri; Silvia Genovese; Maria Lisa Dentici; Stefano Petrocchi; Adriano Angioni; Maria Cristina Digilio; Bruno Dallapiccola Journal: BMC Med Genet Date: 2015-09-03 Impact factor: 2.103