Blonterstaping. Perplisteronk. Contramponist. People who have trouble remembering and repeating nonsense words like these have a common speech and language disorder called specific language impairment (SLI). Although SLI clearly runs in families, the genes responsible have been hard to pin down. Now, a group has found the first such gene, one that had been previously tied to a language disorder in autism. "This study is an important scratch on the surface of the genetics of language impairment," says Mabel Rice, a leading researcher of language disorders and genetics at the University of Kansas, Lawrence.
Molecular neuroscientist Simon Fisher of the University of Oxford in the U.K. and his co-workers received international attention in 2001 when they discovered the first connection between a gene, FOXP2, and a speech and language disorder (ScienceNOW, 3 October 2001). They showed that a rare mutation in FOXP2 explains problems that beset several generations of a British family. Many researchers expected to find direct links between FOXP2 and more common language problems, but none surfaced.
The reason is that FOXP2 is likely one of several genes that work in concert to support speech and language. Fisher's team knew that FOXP2 turned other genes on and off in the brain, so they investigated human neurons grown in the lab to see which parts of the genome were bound by FOXP2 protein. They quickly discovered that FOXP2 had a strong attraction for sections of DNA that controlled a gene called CNTNAP2, which codes for a protein that affects how neurons interact with each other during development, the team reports online today in the New England Journal of Medicine.
Next, the researchers sifted through a database of DNA from 847 people in 184 families that have SLI. They discovered small variations in CNTNAP2 that were significantly associated with SLI, which affects up to 7% of children. "It's the first time we've been able to pin down a particular gene that's involved in common forms of language impairment," says Fisher.
Adding further support to the intersection of CNTNAP2 and language, Fisher's collaborator Daniel Geschwind of the University of California, Los Angeles, reported in January on an association between a variation in the gene and a delay in the use of first words in children with autism. "That's lots of convergent evidence suggesting that CNTNAP2 is involved in SLI," says Fisher.
Fisher would ultimately like his work to be used to help develop a genetic diagnostic test for SLI, which could lead to earlier treatment. Yet he emphasizes that FOXP2 and CNTNAP2 are but two words in a long sentence that remains a mystery. "Not every target that FOXP2 regulates is going to be involved in SLI, and the flip side is this is not the only one," says Fisher. Rice cautions that this study "is the very beginning, not the conclusion, of the mapping of the genetics of language impairment."