UCLA scientists identify genetic link to autism

By Elaine Schmidt

UCLA researchers have identified a new gene linked to autism. The gene — contactin-associated protein-like 2 (CNTNAP2) — is most active in developing brain structures involved with language and thought and appears to be involved in language onset, the researchers found.

Interestingly, evidence for the genetic link came from the DNA of families with autistic boys, not those with autistic girls — which may help to explain why autism strikes boys more often than girls.

Children normally utter their first word by age 1. Children with autism, however, can be speech-delayed by many months or even years. Some never speak at all. Late language onset is a symptom shared by most children with autism.

"This gene not only may predispose children to autism," said Daniel Geschwind, the study's principal investigator and Gordon and Virginia MacDonald Distinguished Professor of Human Genetics at the David Geffen School of Medicine at UCLA. "It also may influence the development of brain structures involved in language, providing a tangible link between genes, the brain and behavior."

The American Journal of Human Genetics publishes the findings today in its online edition, which also features two studies, from research teams at Yale University and Johns Hopkins University, that used different methods that pinpointed the same gene. The coincidences suggest that (CNTNAP2) likely plays a key role in the development of autism.

In an earlier study, the UCLA investigators studied the DNA of 291 families nationwide who had donated blood samples to the Los Angeles-based Autism Genetic Resource Exchange. Each family had at least one autistic child; youngsters who had never spoken were excluded. The findings connected a specific region of chromosome 7 known as 7q35 to autism.

In the current study, the researchers scrutinized every gene in the 7q35 region using DNA samples from 172 families. They identified four promising genes; one of the candidates was CNTNAP2. In a second test of 304 families, the gene showed up consistently, confirming its implication in language development.

The researchers also studied early brain tissue and discovered that the gene was most active in developing brain structures involved in language and thought. "The fact that we found CNTNAP2 concentrated in the brain's structures that are involved in higher cognition gives us strong clues about how its disruption might adversely shape brain development, including speech and language," said UCLA postdoctoral fellow Brett Abrahams, who led this part of the research.

In more autistic boys' families than girls'

In an unexpected finding, the scientists found that statistical evidence for the gene was strongest in families with autistic boys. Less of an association appeared in families with autistic boys and girls, or in families with autistic girls only. "Autism strikes boys up to four times more often than girls," said Maricela Alarcon, first author and a UCLA assistant professor-in-residence of neurology. "This finding may partly explain why."

The gender ratio between boys and girls also applies to rates of attention deficit disorders, learning disabilities and language disorders.

"It will be interesting to learn whether CNTNAP2 also plays a role in language development in non-autistic children," Alarcon said. "Our next step will be to identify more traits, such as seizures or other symptoms, that will help us track down additional genes linked to the disorder."