By following clues left by thalidomide--the drug that caused infamous birth-defects--researchers have identified a gene on chromosome 7 that may be responsible for some cases of autism. Meanwhile, another study has shown that a long stretch of chromosome 15 may hold even more genes that predispose kids to the disorder.
Autism afflicts about 1 in every 500 children, leaving them unable to relate to other people or communicate and causing repetitive and stereotyped behavior and, frequently, mental retardation. Researchers have implicated at least three and perhaps as many as 15 genes in the disorder, and they suspect that toxic chemicals may also play a role.
Studies of thalidomide victims have revealed high rates of autism and malformations in the face and ears among those exposed to the drug in the fourth week of gestation. Similar brain and facial defects show up in mice engineered to lack HOXA1, a gene known to be involved in early development. That's why a team led by Patricia Rodier at the University of Rochester in New York decided to look for a mutation in HOXA1 in humans.
Of 57 autistic patients tested by the team, almost 40% had a mutation in one copy of the gene (one of them had mutations in both). Among 166 family members who were also tested, more than one-third had the mutation, and those who did were more likely to have mild versions of autistic traits. Among 225 nonrelated controls, only about 25% had the altered gene, the team reports in the December issue of Teratology.
The study is a "very significant scientific accomplishment," says Marie Bristol-Power, who chairs the autism coordinating committee at the National Institutes of Health (NIH) in Bethesda, Maryland. Neuropathological data has shown that whatever happens in autism happens in the first 7 months of gestation. This research helps narrow down the time window to the first 3 to 4 weeks, she says.
Another discovery appears in the December issue of the American Journal of Medical Genetics. Researchers led by Anne Spence and Moyra Smith at the University of California, Irvine, report that an autistic 7-year-old girl is missing a stretch of about 1 million base pairs on one of the copies of chromosome 15. Earlier linkage studies also highlighted that area of the chromosome, so genes that normally lie within the missing area are obvious candidates that may play a role in autism, the team concludes.
NIH's autism network, consisting of 10 research programs at different institutions, can now screen more people for HOXA1 and narrow down the search on the chromosome 15 stretch, Bristol-Power says. Eventually, the work may lead to new tests that could predict whether a fetus is at risk for autism, or even drugs to treat the condition, she adds.