title: Xq25 duplications encompassing GRIA3 and STAG2 genes in two families convey recognizable X-linked intellectual disability with distinctive facial appearance.
abstract: We report here on two patients with Xq25 duplication encompassing GRIA3 gene, encoding glutamate receptor, ionotropic, AMPA subunit 3. The first case of Xq25 duplication was identified using genome-wide array comparative genomic hybridization (array-CGH) in a 24-year-old patient with syndromic intellectual disability. Based on similar facial features, we clinically suspected a second case of Xq25 duplication in a 4-year-old boy with intellectual disabilty. This duplication was confirmed by multiplex ligation-dependent probe amplification (MLPA) of the GRIA3 gene, as well as by fluorescence in situ hybridization (FISH) and further refined by array-CGH. We suggest that Xq25 duplication is responsible for a novel clinically recognizable X-linked intellectual disability. Finally, the review of so far published Xq25 duplications support, in addition to the role of GRIA3 gene, a potential contribution of the duplication of STAG2 (Stromal Antigen 2) gene coding for the subunit SA1 of the cohesin complex in the clinical phenotype.
authors: Université Paris Descartes, INSERM U 781 & Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France. anne.philippe@inserm.fr
authors: Anne
authors: A
authors: Philippe
authors: Valérie
authors: V
authors: Malan
authors: Marie-Line
authors: ML
authors: Jacquemont
authors: Nathalie
authors: N
authors: Boddaert
authors: Jean-Paul
authors: JP
authors: Bonnefont
authors: Sylvie
authors: S
authors: Odent
authors: Arnold
authors: A
authors: Munnich
authors: Laurence
authors: L
authors: Colleaux
authors: Valérie
authors: V
authors: Cormier-Daire
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D034961:Antigens, Nuclear / Q000235:genetics*; D001921:Brain / Q000473:pathology; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000000981:diagnostic imaging / Q000235:genetics; D055028:Comparative Genomic Hybridization; D020440:Gene Duplication; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D010641:Phenotype; D011859:Radiography; D018091:Receptors, AMPA / Q000235:genetics*; D012729:Sex Chromosome Aberrations; D014314:Trisomy / Q000235:genetics*; D055815:Young Adult; D000097722:Cohesins
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D018091:Receptors, AMPA; C508565:STAG2 protein, human; D000097722:Cohesins; C104723:glutamate receptor ionotropic, AMPA 3