No association between the WNT2 gene and autistic disorder

Autistic disorder is a pervasive neurodevelopmental disorder characterized by deficits in language and social communication, as well as stereotyped patterns of behavior. Peak LOD scores from several genomic screening efforts indicate the presence of an autistic disorder susceptibility locus within the distal long arm of human chromosome 7 (7q31-q35). Wassink et al. [2001: Am J Med Genet 105:406-413] reported that WNT2, located at 7q31, influences genetic risk in autistic disorder. These findings were enhanced when examined in a subset of families with severe language impairment. WNT genes encode secreted growth factor-like proteins that participate in growth regulation, differentiation, and tumorigenesis. We tested for genetic association of two WNT2 variants in an independent data set of 135 singleton and 82 multiplex families. No significant association was found between autistic disorder and the WNT2 genotypes in either the overall data set or in the language-impaired subset of families. However, differences in allele frequencies of the 3' UTR single nucleotide polymorphism between the present population and that of Wassink et al. may account for the inability to detect association between WNT2 and autistic disorder in the present data set. We also screened the two reported autistic disorder mutations previously detected by Wassink et al. We did not identify any activating mutation in the coding region of the WNT2 gene. Thus, we conclude that activating mutations of the WNT2 gene are not a major contributor to the development of autistic disorder in these data.