From Our 2010 Archives

First Gene Variants Linked to Stuttering Discovered

By Amanda Gardner
HealthDay Reporter

WEDNESDAY, Feb. 10 (HealthDay News) -- Researchers have identified the first gene mutations linked to stuttering.

Surprisingly, the three genes are also linked to some very severe and rare metabolic disorders, but most stutterers are only affected by the speech problem. The researchers estimate that these mutations account for about 9% of stuttering cases.

"This is the first gene information that will tell somebody that they're predisposed to develop this type of stuttering," said Dr. Robert Marion, director of the Center for Congenital Disorders at the Children's Hospital at Montefiore Medical Center in New York City. He was not involved in the study.

"At one point, we may be able to find these mutations and predict that this child with this mutation in this particular gene is likely to go on to develop stuttering," continued Marion, who authored Genetic Rounds: A Doctor's Encounters in the Field That Revolutionized Medicine. "The thinking would be that if we got a kid in speech therapy early on in life, it might prevent this from happening."

"Current therapies are limited in their effectiveness because they're all undertaken without understanding of what causes the disorder," added Dennis Drayna, senior author of the paper, which is published online Feb. 10 in the New England Journal of Medicine. "Now that we know what causes stuttering, we can think about more strategic ways of designing therapies."

Further down the line, enzyme replacement therapy may even be an option.

"Basically, you just give the normal enzyme back to the body," explained Drayna, who is a section chief at the National Institute on Deafness and Other Communication Disorders. "Enzyme therapy has been shown to be safe, but it's the distant future."

Investigators have long suspected that stuttering has a strong genetic component. Roughly 3 million Americans are affected by stuttering, according to background information in the study.

"There's been a sense for a long time that stuttering is an inherited condition. It seems to cluster in families," Marion said.

The researchers analyzed a section of chromosome 12 in a large Pakistani family that had been included in an earlier study by the same researchers.

As it turned out, several mutations in the GNPTAB, GNPTG and NAGPA genes were present in people who stuttered but not in other study participants.

"This gene is involved in a process where the waste products of the cell are removed from the cell and processed in something called a lysosome, which is kind of the garbage can of the cell, the organelle that takes all the waste out of the cell and processes it so the cell doesn't poison itself," explained Marion.

That finding was unexpected, said Drayna. Why would genes regulating this kind of metabolic pathway be involved in stuttering?

"We think a special group of cells in the brain are particularly sensitive to these subtle mutations in these genes," Drayna said. "The mutations that also cause these very serious diseases wipe out the gene so none of the gene product is effectively made. Our mutations probably allow the gene product to be made but it probably doesn't work quite right. It's like a car that needs a tune-up. It still runs but not quite right," Drayna noted.

"Some cells in the body need this to run like a Ferrari in order to function properly and those cells are involved in the production of speech in the brain," he continued.

"That's the biggest scientific breakthrough in these findings. We now have a way, finally, to get at these cells and structures in the brain that are responsible for speech, which heretofore have been very difficult to study and not well understood," Drayna said.

"We have now a bunch of new experiments underway to try to prove or disprove this," he added.

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SOURCES: Dennis Drayna, Ph.D., section chief, National Institute on Deafness and Other Communication Disorders, Bethesda, Md.; Robert Marion, M.D., chief, genetics and development medicine, and director, Center for Congenital Disorders, Children's Hospital at Montefiore Medical Center, New York City, and author Genetic Rounds: A Doctor's Encounters in the Field That Revolutionized Medicine; Feb. 10, 2010, New England Journal of Medicine, online