title: Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
abstract: Autism spectrum disorders (ASDs) are a heterogeneous group of neuro-developmental disorders. While significant progress has been made in the identification of genes and copy number variants associated with syndromic autism, little is known to date about the etiology of idiopathic non-syndromic autism. Sanger sequencing of 21 known autism susceptibility genes in 339 individuals with high-functioning, idiopathic ASD revealed de novo mutations in at least one of these genes in 6 of 339 probands (1.8%). Additionally, multiple events of oligogenic heterozygosity were seen, affecting 23 of 339 probands (6.8%). Screening of a control population for novel coding variants in CACNA1C, CDKL5, HOXA1, SHANK3, TSC1, TSC2 and UBE3A by the same sequencing technology revealed that controls were carriers of oligogenic heterozygous events at significantly (P < 0.01) lower rate, suggesting oligogenic heterozygosity as a new potential mechanism in the pathogenesis of ASDs.
authors.affiliation: Department of Molecular and Human Genetics, Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
authors.forename: Aniko
authors.initials: A
authors.lastname: Sabo
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.forename: Jacy
authors.initials: J
authors.lastname: Crosby
authors.forename: Donna
authors.initials: D
authors.lastname: Muzny
authors.forename: Alicia
authors.initials: A
authors.lastname: Hawes
authors.forename: Lora
authors.initials: L
authors.lastname: Lewis
authors.forename: Humeira
authors.initials: H
authors.lastname: Akbar
authors.forename: Robin
authors.initials: R
authors.lastname: Varghese
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation