Mapping of partially overlapping de novo deletions across an autism susceptibility region (AUTS5) in two unrelated individuals affected by developmental delays with communication impairment.

Autism is a neurodevelopmental disorder characterized by deficits in reciprocal social interaction and communication, and repetitive and stereotyped behaviors and interests. Previous genetic studies of autism have shown evidence of linkage to chromosomes 2q, 3q, 7q, 11p, 16p, and 17q. However, the complexity and heterogeneity of the disorder have limited the success of candidate gene studies. It is estimated that 5% of the autistic population carry structural chromosome abnormalities. This article describes the molecular cytogenetic characterization of two chromosome 2q deletions in unrelated individuals, one of whom lies in the autistic spectrum. Both patients are affected by developmental disorders with language delay and communication difficulties. Previous karyotype analyses described the deletions as [46,XX,del(2)(q24.1q24.2)dn]. Breakpoint refinement by FISH mapping revealed the two deletions to overlap by approximately 1.1Mb of chromosome 2q24.1, a region which contains just one gene—potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3). However, a mutation screen of this gene in 47 autistic probands indicated that coding variants in this gene are unlikely to underlie the linkage between autism and chromosome 2q. Nevertheless, it remains possible that variants in the flanking genes may underlie evidence of linkage at this locus