Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech.
A new study being conducted at the National Institute on Deafness and Other Communication Disorders (NIDCD) has recently found that a defect in the process that cells use to move proteins to their correct locations or intracellular trafficking looks to be the basis of stuttering disorders. The article was published in the American Journal of Human Genetics and extends the findings of previous studies to provide us with an insight into the molecular underpinnings of this neurological disorder.
“Stuttering affects people of all ages and begins most frequently in young children between the ages of 2 and 6, as they are developing their language skills. Most children outgrow stuttering but many do not. Researchers estimate that as many as 1 percent of Americans, roughly 3 million people, live with persistent stuttering. While the exact causes of stuttering are unknown, scientists believe that it stems from problems with the circuits in the brain that control speech.”
Often for people who stutter there is a family history of stuttering with genetics contributing to 80% of cases. Stuttering tends to run in families, and researchers estimate that the contribution of genetic factors to stuttering range as high as 80 percent. A study done by Denis Drayna at the NIDCD linked 3 related genes to stuttering and all three are involved in intracellular trafficking. These genes direct proteins to compartments in order to be broken down and have their components recycled. These genes however only contribute to 8 to 16 percent of inherited stuttering cases therefore further research was required to determine the cause for the remaining majority of cases.
“In the current study, Drayna’s team set out to identify other genes involved in stuttering by focusing on a large family from Cameroon, West Africa, that had many cases of stuttering. The researchers identified mutations in a gene called AP4E1 that are present in individuals in this family who stutter but that did not exist anywhere else in the world, except in two other Cameroonians who were unrelated to this family and who stutter. Other mutations in this gene were subsequently found in individuals who stutter from Brazil, the United States, England, Pakistan, and Cameroon. Like the stuttering genes Drayna’s team discovered earlier, AP4E1, which is a component of a four-part complex, plays a role in intracellular trafficking. Using biochemical methods, the scientists found that the AP4E1 complex physically interacts with one of the previously identified stuttering-associated proteins, suggesting that they work together closely to steer proteins to their proper cellular destinations.”
The two studies combined seem to point firmly at intracellular trafficking defects being the cause of persistent stuttering, more specifically during the process of directing proteins to the cell’s recycling compartment. These same defects have also been linked to other neurological disorders including amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and Alzheimer’s disease, which may possibly be due to certain nerve cell pathways having a particular sensitivity to the process being impaired. This does not imply however, that persistent stuttering is an early indicator of the aforementioned disorders.
“I think one of the most important aspects of our work is that it shows that stuttering, at its source, is a biological problem,” said Drayna. “In the future, we may be able to build on what we’ve learned about the genetics of stuttering to develop novel diagnostics and therapies.”