Studies link autism to two genetic defects
Researchers this week identified two separate genetic defects linked to autism, one that directly causes the disorder in about 1% of cases and a second that may play a role in a much larger percentage of patients by increasing their susceptibility to environmental or other genetic influences.
The findings offer hope that it may be possible to identify vulnerable children early in life and begin treatment to mitigate the effects of the disabling disorder, which is marked by impaired communication and social interaction. Autism disorders are thought to affect 1 in 150 U.S. children.
In the first study, headed by geneticist Mark J. Daly of Massachusetts General Hospital, a multicenter team called the Autism Consortium reported Thursday in the New England Journal of Medicine that deletions or duplications of a specific segment of chromosome 16 increases the risk of autism one-hundredfold.
The genetic defect was found in children with autism but not in their parents, indicating that it was a spontaneous mutation that occurred sometime after fertilization. The location, called 16p11.2, is what is known as a genetic “hot spot,” meaning it is unusually susceptible to such mutations.
The deletions or repetitions were found in 24 of 2,252 people in families with at least one autistic member but in only two out of 18,834 people without the disorder.
The team is now trying to identify the specific gene involved.
The second defect was originally identified in 2006 in four Amish children. Three groups of researchers independently reported Friday in the American Journal of Human Genetics that they had identified the same defect in much larger groups of subjects.
The gene they found is called contactin-associated protein-like 2, or CNTNAP2, which produces a protein that allows brain cells to communicate with one another.
“This gene not only may predispose children to autism,” said one of the researchers, Dr. Daniel Geschwind of UCLA’s David Geffen School of Medicine, “it may also influence the development of brain structures involved in language, providing a tangible link between genes, the brain and behavior.”
Although the mutated form could be inherited from either parent, children were about 20% more likely to develop autism if they inherited the gene from their mother.
“We found a factor that is probably present in every autistic kid,” said geneticist Aravinda Chakravarti of the Johns Hopkins University School of Medicine, who led one of the studies. “But while it may be necessary, it is not sufficient by itself to cause the disease.”
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