title: High frequency of neurexin 1beta signal peptide structural variants in patients with autism.
abstract: Neuroligins are postsynaptic membrane cell-adhesion molecules which bind to beta-neurexins, a family of proteins that act as neuronal cell surface receptors. To explore the possibility that structural variants in the beta-neurexin genes predispose to autism, the coding regions and associated splice junctions of three beta-neurexin genes were scanned with detection of virtually all mutations-SSCP (DOVAM-S) in 72 Caucasian patients with autism. In addition, segments of the neurexin 1beta gene were sequenced in 131 additional Caucasian and 61 Afro-American patients with autism from South Carolina and the Midwest. Two putative missense structural variants were identified in the neurexin 1beta gene in four Caucasian patients with autism and not in 535 healthy Caucasian controls (4/203 vs. 0/535, P=0.0056). Initial family data suggest that incomplete penetrance may occur. In addition, no structural variant was found in the neurexin 2beta gene and the neurexin 3beta gene. In the context of all available data, we conclude that mutations of the neurexin 1beta gene may contribute to autism susceptibility.
authors.affiliation: Department of Molecular Genetics, City of Hope National Medical Center, Duarte, CA 91010-3000, USA.
authors.forename: Jinong
authors.initials: J
authors.lastname: Feng
authors.forename: Richard
authors.initials: R
authors.lastname: Schroer
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Wenjia
authors.initials: W
authors.lastname: Song
authors.forename: Chunmei
authors.initials: C
authors.lastname: Yang
authors.forename: Anke
authors.initials: A
authors.lastname: Bockholt
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Cindy
authors.initials: C
authors.lastname: Skinner
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Steve S
authors.initials: SS
authors.lastname: Sommer
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000523:psychology; D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D004251:DNA Transposable Elements / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019683:Penetrance; D018807:Polymorphism, Single-Stranded Conformational; D011569:Psychiatric Status Rating Scales; D014481:United States / Q000453:epidemiology
chemical_list: D004251:DNA Transposable Elements; D009419:Nerve Tissue Proteins; C086959:neurexin Ibeta