Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation

The 22q13 deletion syndrome is associated with global developmental delay, absent or delayed speech, and generalised hypotonia. In this study, the size and nature of 22q13 deletions (n=9) were studied in detail by high-resolution chromosome specific array-based comparative genomic hybridisation (array CGH). The deletion sizes varied considerably between the different patients, that is, the largest deletion spanning 8.4 Mb with the breakpoint mapping to 22q13.2 and the smallest deletion spanning 3.3 Mb with the breakpoint mapping to 22q13.31. In one case, a unique subtelomeric 3.9 Mb deletion associated with a 2.0 Mb duplication of 22q13 was observed, adding to a growing number of similar cases identified for other chromosome ends. Remarkably, this patient had signs suggestive of retinitis pigmentosa, which has never been reported before in the 22q13 deletion syndrome. The identification of two pairs of recurrent proximal breakpoints on 22q13 suggests that these specific regions may be prone to recombination, due to yet unknown genome architectural features. In addition to the copy number changes on 22q13, a duplication of approximately 330 kb on 22q11.1 was observed and shown to be a genetic large-scale copy number variation without clinical consequences. The current study failed to reveal relationships between the clinical features and the deletion sizes. Global developmental delay and absent or severely delayed speech were observed in all patients, whereas hypotonia was present in 89% of the cases (8/9). This study underscores the utility of array CGH for characterising the size and nature of subtelomeric deletions, such as monosomy 22q13, and underlines the considerable variability in deletion size in the 22q13 deletion syndrome regardless of the clinical phenotype.