Xq25 duplications encompassing GRIA3 and STAG2 genes in two families convey recognizable X-linked intellectual disability with distinctive facial appearance


INSERM U781, Département de Génétique Médicale, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris 75015, France. E-mail: anne.philippe@inserm.fr


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. © 2012 Wiley Periodicals, Inc.