Researchers at Washington University School of Medicine in St. Louis have obtained new evidence that at least some persistent stuttering is caused by mutations in a gene governing not speech, but a metabolic pathway involved in recycling old cell parts.
Beyond a simple association, the study provides the first evidence that mutations affecting cellular recycling centers called lysosomes actually play a role in causing some people to stutter.
"This was extremely unexpected," says senior author Stuart A. Kornfeld, MD, the David C. and Betty Farrell Professor of Medicine. "Why would impairment in a lysosomal pathway lead to stuttering? We don't know the answer to that. Partly because we don't know very much about the mechanisms of speech, including which neurons in the brain are involved. So we can't fully explain stuttering, but now we have clues."
The research is available online in the Journal of Biological Chemistry.
Genetic clues to stuttering were first identified in a paper published in the New England Journal of Medicine in February 2010. In it, Dennis Drayna, PhD, a senior investigator with the National Institute on Deafness and Other Communication Disorders and a co-author on the current study, and his colleagues reported results of genetic studies on members of a large Pakistani family, many of whom stutter.
Among most of the stuttering family members, they found mutations in three genes involved in directing proteins to the lysosome. These same mutations were present in many unrelated individuals in Pakistan, North America and Europe who stutter, but not in those with normal speech.
"They found mutations in three genes that encode a pathway for directing newly made lysosomal enzymes to the lysosomes," Kornfeld says. "And it turned out to be a pathway we discovered years ago. So this is a nice collaboration."
Until now, one of the three genes, NAGPA, had not been implicated in
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Washington University School of Medicine