Frameshift and missense mutations in the X-linked
neuroligin 4 (NLGN4, MIM# 300427) and
neuroligin 3 (NLGN3, MIM# 300336) genes have been identified in patients with
autism,
Asperger syndrome and
mental retardation. We hypothesize that sequence variants in NLGN4Y are associated with
autism or
mental retardation. The coding sequences and splice junctions of the NLGN4Y gene were analyzed in 335 male samples (290 with
autism and 45 with
mental retardation). A total of 1.1 Mb of genomic
DNA was sequenced. One missense variant, p.I679V, was identified in a patient with
autism, as well as his father with
learning disabilities. The I679 residue is highly conserved in three members of the
neuroligin family. The absence of p.I679V in 2986 control Y chromosomes and the high similarity of NLGN4 and NLGN4Y are consistent with the hypothesis that p.I679V contributes to the etiology of
autism. The presence of only one structural variant in our population of 335 males with
autism/
mental retardation, the unavailability of significant family cosegregation and an absence of functional assays are, however, important limitations of this study.