Article Text

Download PDFPDF
Detection of known and novel genomic rearrangements by array based comparative genomic hybridisation: deletion of ZNF533 and duplication of CHARGE syndrome genes

Abstract

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.

View Full Text

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.