1. ¹The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
2. ²INSERM U781 and Département de Génétique, Hôpital Necker-Enfants Malades, rue de Sèvres, Paris, France

Correspondence: Dr L Colleaux, INSERM U781, Hôpital Necker – Enfants Malades, Tour Lavoisier, 149 rue de Sèvres, 75015 Paris, France. Tel: +33 1 44 49 51 60; Fax: +33 1 47 34 85 14; E-mail: colleaux@necker.fr

³These authors equally contributed to the work

Received 25 October 2005; Revised 9 February 2006; Accepted 10 February 2006; Published online 29 March 2006.

Abstract

In the course of a systematic whole genome screening of patients with unexplained overgrowth syndrome by microarray-based comparative genomic hybridisation (array-CGH), we have identified two children with nearly identical 6.5 Mb-long de novo interstitial deletions at 9q22.32–q22.33. The clinical phenotype includes macrocephaly, overgrowth and trigonocephaly. In addition, both children present with psychomotor delay, hyperactivity and distinctive facial features. Further analysis with a high-resolution custom microarray covering the whole breakpoint intervals with fosmids mapped the deletion breakpoints within 100-kb intervals: although the deletion boundaries are different for the two patients, nearly the same genes are deleted in both cases. We suggest therefore that microdeletion of 9q22.32–q22.33 is a novel cause of overgrowth and mental retardation. Its association with distinctive facial features should help in recognising this novel phenotype.