title: Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder.
abstract: Autism spectrum disorders (ASDs) 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 bacterial artificial chromosome (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 out of 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 copy number variants 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.
authors.affiliation: Unitat de Genètica, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Ivon
authors.initials: I
authors.lastname: Cuscó
authors.forename: Andrés
authors.initials: A
authors.lastname: Medrano
authors.forename: Blanca
authors.initials: B
authors.lastname: Gener
authors.forename: Mireia
authors.initials: M
authors.lastname: Vilardell
authors.forename: Fátima
authors.initials: F
authors.lastname: Gallastegui
authors.forename: Olaya
authors.initials: O
authors.lastname: Villa
authors.forename: Eva
authors.initials: E
authors.lastname: González
authors.forename: Benjamín
authors.initials: B
authors.lastname: Rodríguez-Santiago
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
authors.forename: Miguel
authors.initials: M
authors.lastname: Del Campo
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Jurado
mesh_terms: D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D018628:Gene Dosage; D006801:Humans; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D010716:Phosphatidylinositols