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Multiple genetic 'flavors' may explain autism

While debate still rages over the 'cause' of autism, mounting evidence suggests that genetic factors play a major role in the disease. Two recent studies led by James Sutcliffe, Ph.D., and Randy Blakely, Ph.D., investigators with the Vanderbilt Center for Molecular Neuroscience and the Vanderbilt Kennedy Center for Research on Human Development, suggest that multiple rare mutations within a single gene may increase risk for autism. Their findings also may point to new therapeutic options for this devastating disorder.

In this pair of studies, the researchers identify and characterize a number of mutations in the gene that regulate brain levels of serotonin, a neurotransmitter involved in many biological processes including breathing, digestion, sleep, appetite, blood vessel constriction, mood and impulsivity.

About 25 percent of people with autism have elevated levels of serotonin in their blood. Selective serotonin reuptake inhibitors (SSRIs), drugs used to treat depression, anxiety and obsessive-compulsive disorders, also improve some of the symptoms of the disorder. These findings have led scientists to propose that serotonin plays an important role in autism.

In the August issue of the American Journal of Human Genetics, Sutcliffe, Blakely and colleagues report that several mutations within the serotonin transporter (SERT) gene, which regulates serotonin levels in the brain, may be risk factors for autism.

One variation in the SERT gene has been extensively studied and previously led to an inconclusive association to autism. No other variation stood out as a strong risk factor for the disease. Sutcliffe's own work had detected a strong linkage between autism and a 'spot' on chromosome 17 the neighborhood where the SERT gene resides. A few common variants or versions of this gene were known, but did not seem to impart increased risk of autism.

"We failed to see evidence for a common version of the SERT gene that is the
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Contact: Clinton Colmenares
clinton.colmenares@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
25-Jul-2005


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