Genes Behind Stuttering Found

LiveScience Staff

Date: 10 February 2010 Time: 12:00 PM ET

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The epigenome is a molecular marking system that controls gene expression without altering the DNA sequence. In a sense, the epigenome is the genome's boss. Image CREDIT: Dreamstime

Stuttering may have genetic underpinnings, according to a new study. For the first time, scientists have identified specific genetic alterations that they believe play a key role in giving rise to the speech disorder.

These alterations, or mutations, are located on three particular genes, and are thought to cause a glitch in the way cells dispose of cellular "garbage."

"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 Dr. James F. Battey, Jr., director of the National Institute on Deafness and Other Communication Disorders (NIDCD), the organization that led the study. "This is the first study to pinpoint specific gene mutations as the potential cause of stuttering," and might lead to an expansion in treatment options, he said.

The results were published online Feb. 10 in the New England Journal of Medicine.

Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech. The result can severely hinder communication. Most children who stutter outgrow it, although many do not; roughly 1 percent of adults stutter worldwide. Current therapies for adults who stutter have focused on such strategies as reducing anxiety, regulating breathing and rate of speech, and using electronic devices to help improve fluency.

Stuttering tends to run in families, and researchers have long suspected a genetic component. Previous studies of a group of families from Pakistan pointed to chromosome 12 as a site that may be involved in the disorder. (A chromosome is a long sequence of DNA that contains many genes.)

In the current study, researchers took a closer look at this chromosome. They identified mutations in a gene known as GNPTAB in the affected family members. The GNPTAB gene is carried by all higher animals, and gives cells instructions for making an enzyme that assists in breaking down and recycling cellular components.

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. The researchers found some individuals who stutter possessed the same mutation as that found in the large Pakistani family.

The scientists then looked at two other genes which are closely tied to the role of GNPTAB. They found individuals who stuttered showed mutations in these genes while control groups did not.

Several of the newly identified "stuttering genes" are thought to contribute to certain metabolic disorders. People with these disorders cannot properly break down cell waste, causing deposits to build up in their cells. These deposits can ultimately cause health problems in the body's joints, skeletal system, heart and liver, as well as developmental problems in the brain. They are also known to cause problems with speech.

So why don't people who stutter also have these metabolic disorders? For many of these metabolic diseases, a person needs to have two defective copies of a gene, said study author Dennis Drayna, a geneticist with the NIDCD. But in the current study, nearly all of the unrelated individuals who stuttered had only one copy of the mutated gene, he said.

The findings open new research avenues into possible treatments for stuttering. For example, current treatment methods for some metabolic disorders involve injecting a manufactured enzyme into a person's bloodstream to replace the missing enzyme. The researchers wonder if enzyme replacement therapy might be a possible method for treating some types of stuttering in the future.

Right now, about 9 percent of people who stutter are known to possess mutations in one of the three genes, the researchers say. Next, they plan to conduct a worldwide study to better determine the number of people who carry these mutations. A long-term goal is to better understand how metabolic defects may affect structures within the brain that are essential for fluent speech.