London, Feb 11 (ANI): Researchers at the National Institute on Deafness and Other Communication Disorders have identified three genes as a source of stuttering in volunteers in Pakistan, the United States, and England.
Published in the Feb. 10 Online First issue of the New England Journal of Medicine, the study says stuttering may be the result of a glitch in the day-to-day process by which cellular components in key regions of the brain are broken down and recycled.
Mutations in two of the genes have already been implicated in other rare metabolic disorders also involved in cell recycling, while mutations in a third, closely related, gene have now been shown to be associated for the first time with a disorder in humans.
"For hundreds of years, the cause of stuttering has remained a mystery for researchers and health care professionals alike, not to mention people who stutter and their families," said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. "This is the first study to pinpoint specific gene mutations as the potential cause of stuttering, a disorder that affects 3 million Americans, and by doing so, might lead to a dramatic expansion in our options for treatment."
Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech.
In the study, Dennis Drayna, Ph.D., a geneticist with the NIDCD, had earlier indicated a place on chromosome 12 that was likely to harbor a gene variant that caused this disorder.
Now, Dr. Drayna and his team refined the location of this place on chromosome 12 and focused their efforts on the new site. They sequenced the genes surrounding a new marker and identified mutations in a gene known as GNPTAB in the affected family members. The GNPTAB gene is carried by all higher animals, and helps encode an enzyme that assists in breaking down and recycling cellular components, a process that takes place inside a cell structure called the lysosome.
They then analyzed the genes of 123 Pakistani individuals who stutter-46 from the original families and 77 who are unrelated-as well as 96 unrelated Pakistanis who don't stutter, and who served as controls. Individuals from the United States and England also took part in the study, 270 who stutter and 276 who don't.
After analyses, researchers found some individuals who stutter possessed the same mutation as that found in the large Pakistani family. They also identified three other mutations in the GNPTAB gene which showed up in several unrelated individuals who stutter but not in the controls.
GNPTAB encodes its enzyme with the help of another gene called GNPTG. In addition, a second enzyme, called NAGPA, acts at the next step in this process. Together, these enzymes make up the signaling mechanism that cells use to steer a variety of enzymes to the lysosome to do their work.
Because of the close relationship among the three genes in this process, the GNPTG and NAGPA genes were the next logical place for the researchers to look for possible mutations in people who stutter. Indeed, when they examined these two genes, they found mutations in individuals who stutter, but not in control groups. (ANI)