Brain gene implicated in autism

Scientists funded by the National Institute of Mental Health have linked a gene that may influence human brain development with autism susceptibility. They pinpointed the candidate gene, WNT2, in a region of chromosome 7 suggested by several studies over the past few years. NIMH grantees Thomas Wassink, M.D., University of Iowa, and Joseph Piven, M.D., University of North Carolina, and colleagues, report on their findings in the American Journal of Medical Genetics , available online May 17, 2001.

Rare mutations in WNT2 may "significantly increase susceptibility to autism," say the researchers, while a common variant may contribute to the disorder to a lesser degree. "While the evidence implicating this gene is good, it's not overwhelming, and must be replicated by other groups," cautioned Wassink.

Affecting 1 in 500 to 1 in 2500 Americans, autism begins in early childhood and impairs thinking, feeling, language and the ability to relate to others. Evidence suggests that the disorder is at least 90 percent heritable, stemming from complex interactions among 3 to 15, or more, genes.

The WNT2 gene attracted the investigators' attention because of its suspect location on chromosome 7 (7q31-33); three recent genome scans had pointed to the region as likely harboring an autism gene. It is a member of a family of 16 WNT genes, a number of which are known to influence brain development. Mice bred without genes essential to the functioning of WNT genes show diminished social interaction, similar to people with autism. Also, WNT2 is located next to a broken chromosome in an individual with autism, heightening suspicion of its involvement in the disorder.

Among 135 individuals with autism screened, the researchers identified two families in which mutated variants of WNT2 were found in just one parent and in affected, but not in well, siblings. Both mutations were in coding regions of the gene. No mutated variants of WNT2 were found in 1

Contact: Jules Asher
NIH/National Institute of Mental Health

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