Tuesday, October 17, 2006

Autism Spectrum Disorder gene mutation research

For the first time, researchers have identified a specific gene mutation that increases the risk of autism.
And while scientists are hailing the discovery as significant, they add that it will be many years before the research has medical applications.
The study of more than 700 families with autistic children found that a mutation that decreases the production of a protein designated MET more than doubles the risk of the disorder.
The report, led by researchers at Vanderbilt University in Nashville, Tenn., was published in this week's issue of the Proceedings of the National Academy of Sciences.
"Rare changes in genes have been identified before this as contributing to the risk of autism," said Dr. Matthew W. State, director of the Yale University School of Medicine's program on neurogenetics, who wrote an accompanying commentary in the journal. "Conversely, there have been a number of instances where a gene has been implicated, but where the functional change that led to the finding was not found."
"This time, they have gone all the way, identifying the gene and the mechanism. It is tremendously important because it tells you what the biological processes might be," State added.
Autism is a disorder that causes social deficits, language impairment and repetitive behavior. Its reported incidence has increased sharply in recent years, perhaps because of more awareness of the condition. The incidence of autism itself is estimated at one in every 500 American children, and the rate of autism-related conditions is as high as one in 166.
The MET protein studied by the researchers has many roles in the body. It is best known for promoting metastasis, the spread of a variety of cancers. But it also has been found to contribute to immune function and gastrointestinal repair. Recent studies, by the Vanderbilt group and others, have shown that the protein contributes to development of the cerebral cortex and cerebellum, parts of the brain that can be abnormal in people with autism.
This study found that a mutation of the portion of the MET gene that governs the production of its protein was associated with the risk of autism. The strongest association of the mutation to autism was found in families with more than one affected child. Overall, the presence of the mutation raised the risk of autism by 2.27 times.
An essential step now is to verify the finding, said Andy Shih, director of research at the National Alliance for Autism Research.
"Maybe 100 candidate genes have been identified before this, and most of them have not been replicated," Shih said. "But what distinguishes this particular paper is that it involves the biology associated with this condition."
Now that a mutation has been identified, Shih said, "we must try to understand how this functional variant is related to behavioral manifestations."
State said: "The first thing always is that this absolutely must be replicated in other laboratories. Second, in terms of understanding the biology better, we have to take a look at what happens in vivo," meaning in physical function.
One possible method of verifying the finding would be to bioengineer animals such as mice so their production of MET protein is reduced, to see how that affects their behavior, State said.
But, Shih added, any medical application of the finding is many years away.