Abstract

Autism Spectrum Disorder (ASD) is a developmental disorder of the central nervous system of largely unknown etiology. The prevalence of the syndrome underscores the need for biological markers and a clearer understanding of pathogenesis. For these reasons, a genetic study of idiopathic ASD was undertaken. Array-based comparative genomic hybridization identified a paternally inherited chromosome 3 copy number variation (CNV) in 3 subjects: a deletion in 2 siblings and a duplication in a third, unrelated individual. These variations were FISH validated and the endpoints further delineated using a custom fine tiling oligonucleotide array. PCR products unique to the rearrangements were amplified and sequence analysis revealed the variations to have resulted from Alu Y-mediated unequal recombinations interrupting contactin 4 (CNTN4). CNTN4 plays an essential role in the formation, maintenance, and plasticity of neuronal networks. Disruption of this gene is known to cause developmental delay and mental retardation. This report suggests that mutations affecting CNTN4 function may be relevant to ASD pathogenesis.