New Genetic Link To Autism Discovered By Studying Speech

The American Journal of Human Genetics publishes the findings in its Jan. 10 online edition, which also features two studies from research teams at Yale and Johns Hopkins that used different methods that pinpointed the same gene. The coincidence suggests that the gene, called contactin-associated protein-like 2 (CNTNAP2), likely plays a key role in the development of autism.

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

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 language at all. Late language onset is a symptom shared by most children with 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, called 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.

To verify their findings, the scientists conducted a second test on a new group of 304 families. The CNTNAP2 gene showed up consistently, confirming its implication in language development.

In a second approach, the researchers examined CNTNAP2's presence in early brain tissue and discovered that the gene was most active in developing brain structures involved in language and thought.

Postdoctoral fellow Brett Abrahams, who led this part of the research, explains the finding's significance by comparing the brain to a house.

"We know that different rooms in houses serve different purposes," said Abrahams. "For example, if an item only appears in the kitchen, it makes sense to assume it's involved in cooking. Or if we find an object only in the bedroom, it's likely connected to sleeping.

"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," he said.

In an unexpected third 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 three times as often as girls," said Maricela Alarcon, first author and UCLA assistant professor in residence of neurology. "This finding may partly explain why."

The 3:1 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," observed Alarcon. "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."

Coauthors included Jacqueline Duvall, Julia Perederiy, Jamee Bomar, Stanley Nelson and Rita Cantor, all from UCLA. Jennifer Stone of Harvard University, Jonathan Sebat and Michael Wigler of Cold Spring Harbor Laboratory, and Christa Martin and David Ledbetter of Emory University also contributed to the research.

The study was primarily supported with funding from the National Institute of Mental Health, National Institute of Neurological Disease and Stroke, Cure Autism Now Foundation and UCLA Center for Autism Research and Treatment. The authors had no competing financial interests.