Mutations in the genes encoding the presynaptic cell-adhesion molecules, neurexins, and their postsynaptic binding partners, neuroligins, have been implicated in non-syndromic ASDs (Gauthier et al., 2011; Camacho-Garcia et al., 2013; Vaags et al., 2012; Steinberg et al., 2012; Jamain et al., 2003; Feng et al., 2006). Additionally, mutations in genes coding for other members of the neurexin superfamily, contactin associated protein-2 (CNTNAP2; Alarcón et al., 2008; Arking et al., 2008) and contactin associated protein-4 (CNTNAP4; Karayannis et al., 2014), have been identified in cases of ASD. Each of the three neurexin genes (NRXN1, NRXN2, NRXN3) contains two promoters, which generate a longer α-NRXN or a shorter β-NRXN, respectively (Tabuchi and Südhof, 2002). Moreover, the neurexins undergo extensive alternative splicing, resulting in thousands of different isoforms (Ullrich et al., 1995; Treutlein et al., 2014). On the other hand, the neuroligin genes (NLGN1, NLGN2, NLGN3, NLGN4X, NLGN4Y) contain one promoter and two alternatively spliced regions, allowing for up to four different isoforms per gene (Ichtchenko et al., 1996). Together, neurexins and neuroligins form trans-synaptic complexes that facilitate synapse formation and maturation, as well as excitatory and inhibitory transmission (reviewed in Bang and Owczarek, 2013).
