A pathway involved in language development is increasingly proving to be important in autism, suggest a series of new studies on cellular and behavioral aspects of the disorder.

Reports published in the last year, as well as preliminary data revealed last week at the Society for Neuroscience meeting in Chicago add heft to the idea that the pathway may cause the language and other problems associated with autism.

In 1990, a letter to Nature described a large, three-generation family from London whose members had severe and distinct deficits in applying grammatical rules, and suggested “one dominant gene” as the cause. A decade later, geneticists screening the family pinpointed a gene — FOXP2, on chromosome 7 — that is mutated in family members with language impairment.

FOXP2 codes for a protein that regulates the expression of other genes. Last year, an international group of scientists identified one of its targets, contactin-associated protein-like 2 (CNTNAP2). They also found that certain common variants of CNTNAP2 tend to crop up in people with specific language impairment, a developmental disorder.

CNTNAP2 was an exciting find because three independent teams had recently published that common variants of the gene up the risk of developing autism.

“I think the evidence now that CNTNAP2 is involved [in autism] is quite good,” says leader of one of the teams, Aravinda Chakravarti, professor at the McKusick Nathans Institute of Genetic Medicine at Johns Hopkins University. “We’re now interested in finding the molecular basis of this.”

In unpublished data, Chakravarti says he’s found that CNTNAP2 is over-expressed in a small number of postmortem autistic brains.

Geneticists have discovered many different autism-related variants of CNTNAP2, a massive gene spanning 2.3 million base pairs. “Disruptions in the front end of the gene [usually] mean you’ll get a more severe disorder, like full-blown autism or severe expressive language delay,” notes Martin Poot, research associate professor of medical genetics at the University Medical Center Utrecht, in the Netherlands.

In contrast, mutations toward the back end of CNTNAP2 may not lead to a disorder, or could cause Tourette’s syndrome in which, Poot says, people “cannot control their speech and from time to time say all kinds of weird things which they don’t intend to say.”

The front end of CNTNAP2 holds FOXP2 binding sites — suggesting that it’s the combination of disruptions in both genes, and probably others, that leads to full-blown autism, Poot says.

Supporting this idea, this summer Poot’s team identified an 11-year-old boy with autism and speech delay who carries chromosomal deletions and rearrangements in the FOXP2 binding sites on CNTNAP2, as well as in many genes in chromosome 2. The boy is part of a larger study of more than 200 children with autism. So far, Poot has found four children who carry variants in the contactin family of genes.

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