title: Simple detection of genomic microdeletions and microduplications using QMPSF in patients with idiopathic mental retardation.
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.
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France. Pascale.Saugier-Veber@chu-rouen.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Céline
authors.initials: C
authors.lastname: de La Rochebrochard
authors.forename: Valérie
authors.initials: V
authors.lastname: Layet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Drouot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Meur
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gilbert-Du-Ssardier
authors.forename: Géraldine
authors.initials: G
authors.lastname: Joly-Hélas
authors.forename: Hélène
authors.initials: H
authors.lastname: Moirot
authors.forename: Annick
authors.initials: A
authors.lastname: Rossi
authors.forename: Mario
authors.initials: M
authors.lastname: Tosi
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics; D020440:Gene Duplication; D015321:Gene Rearrangement; D015894:Genome, Human; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D015203:Reproducibility of Results; D016615:Telomere / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human