PURPOSE: 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 hybridization allows to detect 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 6,465 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; while 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 were 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 most probably is the fourth zinc-finger gene implied in mental retardation. On the other hand, we propose that CHD7 gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.