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

Neuroligins are postsynaptic membrane cell-adhesion molecules which bind to β-neurexins, a family of proteins that act as neuronal cell surface receptors. To explore the possibility that structural variants in the β-neurexin genes predispose to autism, the coding regions and associated splice junctions of three β-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 1β 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 1β 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 2β gene and the neurexin 3β gene. In the context of all available data, we conclude that mutations of the neurexin 1β gene may contribute to autism susceptibility.