Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental Retardation

Whole-genome analysis using high-density single-nucleotide–polymorphism oligonucleotide arrays allows identification of microdeletions, microduplications, and uniparental disomies. We studied 67 children with unexplained mental retardation with normal karyotypes, as assessed by G-banded chromosome analyses. Their DNAs were analyzed with Affymetrix 100K arrays. We detected 11 copy-number variations that most likely are causative of mental retardation, because they either arose de novo (9 cases) and/or overlapped with known microdeletions (2 cases). The eight deletions and three duplications varied in size from 200 kb to 7.5 Mb. Of the 11 copy-number variations, 5 were flanked by low-copy repeats. Two of those, on chromosomes 15q25.2 and Xp22.31, have not been described before and have a high probability of being causative of new deletion and duplication syndromes, respectively. In one patient, we found a deletion affecting only a single gene, MBD5, which codes for the methyl-CpG-binding domain protein 5. In addition to the 67 children, we investigated 4 mentally retarded children with apparent balanced translocations and detected four deletions at breakpoint regions ranging in size from 1.1 to 14 Mb.