1. ¹Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2. ²National Centre for Medical Genetics, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland
3. ³Department of Clinical Genetics, Institute of Child Health, London, UK
4. ⁴Department of Medical Genetics, CHU Pellegrin, Bordeaux, France
5. ⁵Department of Clinical Genetics, The Churchill Hospital, Oxford, UK
6. ⁶Wessex Regional Genetics Service, The Princess Anne Hospital, Southampton, UK
7. ⁷Department of Medical Physics and Biophysics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence: Dr BBA de Vries, Department of Human Genetics, 417, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands. Tel: +31 24 361 3946; Fax: +31 24 366 8753; E-mail: b.devries@antrg.umcn.nl

Received 25 February 2005; Revised 9 May 2005; Accepted 19 May 2005; Published online 29 June 2005.

Abstract

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 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.