title: Copy number variation characteristics in subpopulations of patients with autism spectrum disorders.
abstract: Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P = 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. anna.bremer@ki.se
authors.forename: Anna
authors.initials: A
authors.lastname: Bremer
authors.forename: MaiBritt
authors.initials: M
authors.lastname: Giacobini
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.forename: Peter
authors.initials: P
authors.lastname: Gustavsson
authors.forename: Viviann
authors.initials: V
authors.lastname: Nordin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Fernell
authors.forename: Christopher
authors.initials: C
authors.lastname: Gillberg
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.forename: Asa
authors.initials: A
authors.lastname: Uppströmer
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Anderlid
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schoumans
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000706:statistics & numerical data; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D009154:Mutation; D010641:Phenotype