Feb. 10, 2010 -- Researchers with the National Institutes of Health (NIH) have identified three genes that may predispose people to stuttering -- a condition that affects 3 million Americans and 5% of young children.
Because stuttering tends to run in families, it has long been suspected that genes play a role in the speech disorder.
The GNPTAB, GNPTG, and NAGPA variants were found in only a small proportion of cases, together accounting for 21 of 393 cases in unrelated, affected subjects — a finding that is consistent with the genetic heterogeneity that underlies stuttering.8,9,10,11 Causative factors in the remaining 95% of cases remain to be elucidated. Because the identified variants are rare, they would have escaped detection on a standard genomewide association screen.
Massive cheap genetic scanning is needed to tease out the many genetic causes of stuttering. The same is true for many other genetically caused disorders. Fortunately genetic testing and sequencing has fallen by orders of magnitude in recent years and the cost declines continue. That's why we are seeing more reports of discoveries of causes of genetically caused disorders. I predict we will soon see a lot of reports about genetic causes of personality and IQ differences because the tools are finally available to collect sufficient amounts of genetic data to discover the causes.
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.
The GNPTAB and GNPTG genes have already been tied to two serious metabolic diseases known as mucolipidosis (ML) II and III. MLII and MLIII are part of a group of diseases called lysosomal storage disorders because improperly recycled cell components accumulate in the lysosome. Large deposits of these substances ultimately cause joint, skeletal system, heart, liver, and other health problems as well as developmental problems in the brain. They are also known to cause problems with speech.
“You might ask, why don’t people with the stuttering mutations have more serious complications? Why don’t they have an ML disease?” posed Dr. Drayna, senior author of the paper. “ML disorders are recessive. You need to have two copies of a defective gene in order to get the disease. Nearly all of the unrelated individuals in our study who stuttered had only one copy of the mutation. Also, with stuttering, the protein is still made, but it’s not made exactly right. With ML diseases, the proteins typically aren’t made at all. Still, there are a few complexities remaining to be understood, and we’d like to learn more about them.”
|Share |||Randall Parker, 2010 February 11 10:26 PM Brain Genetics|