High frequency of neurexin 1β signal peptide structural variants in patients with autism

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 P-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 1 beta 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 1 beta 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 20 gene and the neurexin 3 beta gene. In the context of all available data, we conclude that mutations of the neurexin 1 beta gene may contribute to autism susceptibility. (c) 2006 Elsevier Ireland Ltd. All rights reserved.