Human Molecular Genetics Advance Access published online on February 26, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp092
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Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder
1 Unitat de Genètica, Universitat Pompeu Fabra, Barcelona 08003, Spain 2 CIBER de enfermedades raras (CIBERER), Barcelona 08003, Spain 3 Unidad de Genética Clínica, Hospital de Cruces, Barakaldo, Bizkaia, Spain 4 Centre de Regulació Genòmica (CRG), Barcelona 08003, Spain 5 Hospital Psiquiatric Universitari Institut Pere Mata, Reus, Spain 6 Programa de Medicina Molecular i Genètica, Hospital Vall d'Hebron, Barcelona 08039, Spain
Corresponding author Name: LA Pérez Jurado, MD, PhD Address: Unitat de Genètica, Universitat Pompeu Fabra Parc de Recerca Biomèdica de Barcelona, Dr Aiguader 88 08003 Barcelona Spain Telephone: +34 93 316 0856 Fax: +34 93 316 0901 Email: luis.perez{at}upf.edu
Received December 29, 2008; Revised February 17, 2009; Accepted February 23, 2009
Autism Spectrum Disorders (ASD) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade BAC array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 Kb to 2.4 Mb, were present specifically in the autistic population (12/96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific CNVs act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD.