1. ¹Department of Genetics, Rouen University Hospital, Rouen, France
2. ²Inserm U614, Faculty of Medicine, 22 boulevard Gambetta, Rouen, France
3. ³Department of Cytogenetics, Rouen University Hospital, Rouen, France
4. ⁴Department of Cytogenetics, Le Havre Hospital, Le Havre, France
5. ⁵Department of Genetics, Etablissement Français du Sang, Bois-Guillaume, France
6. ⁶Department of Genetics, Jean Bernard University Hospital, Poitiers, France

Correspondence: Dr P Saugier-Veber, Inserm U614, Faculty of Medicine, 22 boulevard Gambetta, 76183 Rouen, France. Tel: +33 2 32 88 88 58; Fax: +33 2 32 88 80 80; E-mail: Pascale.Saugier-Veber@chu-rouen.fr

Received 1 December 2005; Revised 6 April 2006; Accepted 13 April 2006; Published online 14 June 2006.

Abstract

In contrast to the numerous well-known microdeletion syndromes, only a few microduplications have been described, and this discrepancy may be due in part to methodological bias. In order to facilitate the detection of genomic microdeletions and microduplications, we developed a new assay based on QMPSF (Quantitative Multiplex PCR of Short fluorescent Fragments) able to explore simultaneously 12 candidate loci involved in mental retardation (MR) and known to be the target of genomic rearrangements. We first screened 153 patients with MR and facial dysmorphism associated with malformations, or growth anomalies, or familial history, with cytogenetically normal chromosomes, and the absence of FRAXA mutation and subtelomeric rearrangements. In this series, we found a 5q35 deletion removing the NSD1 gene in a patient with severe epilepsy, profound MR and, retrospectively, craniofacial features of Sotos syndrome. In a second series, we screened 140 patients with MR and behaviour disturbance who did not fulfil the de Vries criteria for subtelomeric rearrangements and who had a normal karyotype and no detectable FRAXA mutation. We detected a 22q11 deletion in a patient with moderate MR, obesity, and facial dysmorphism and a 4 Mb 17p11 duplication in a patient with moderate MR, behaviour disturbance, strabismus, and aspecific facial features. This new QMPSF assay can be gradually upgraded to include additional loci involved in newly recognised microduplication/microdeletion syndromes, and should facilitate wide screenings of patients with idiopathic MR and provide better estimates of the microduplication frequency in the MR population.