Wash. U. Scientists Discover Reason for Stuttering is in the Genes

Dec 6, 2011 at 2:45 pm
Not even Geoffrey Rush and an Oscar can cure your stuttering problem.
Not even Geoffrey Rush and an Oscar can cure your stuttering problem.

If everything you know about stuttering comes from movies such as last year's Oscar-winner The King's Speech, you may be forgiven for believing the speech disorder is the result of a sad childhood and a profound lack of self-confidence and can be cured with help from a wise and understanding speech pathologist and the love of the Queen Mum.

Then again, did you actually believe King George VI looked like Colin Firth?

In any case, a group of researchers at Washington University Medical School recently published a paper in the Journal of Biological Chemistry that shows that stuttering is actually the result of a mutation in a gene that controls -- and here's the surprising part -- not speech, but the recycling process in individual cells.

In other words, the problem of stuttering is infinitely smaller and more complicated than anybody thought. You can't cure it through smoking cigarettes or reciting poetry with pebbles in your mouth or even through modern gene therapy, at least not yet. Isn't that typical?

As the Wash. U. research team led by Dr. Stuart A. Kornfeld and researcher Wang-Sik Lee explains in its paper, published online in the Journal of Biological Chemistry, each cell contains a tiny part, or organelle, called a lysosome, responsible for breaking down cell waste products and either disposing of them or recycling them. Think of it as a very, very tiny digestive system.

The scientists discovered three different mutations in a gene called NAGPA. When NAGPA is functioning normally, it produces an enzyme that performs the last step in sorting which proteins get sent to the lysosome. The mutations, however, keep the enzyme from doing its job and for some reason, yet to be discovered, the misdirected proteins cause people to stutter. The researchers theorize if there was some way to get the gene to function properly and get the proteins to where they ought to be, this may stop the stuttering.

The research is based on genetic studies of non-related stutterers in Pakistan, Europe and North America, all of whom have one of the three mutations. An earlier study of a large Pakistani family with a lot of stutterers, published in the New England Journal of Medicine, identified two other mutations in genes that perform functions similar to that of NAGPA that might also be related to stuttering. The Wash. U. team is now starting to analyze those genes.

Unfortunately, the scientists think they're a long, long way from figuring out why this one little malfunctioning enzyme should cause people to stutter.

"There are billions of neurons in the brain," said Kornfeld, "and we have very little idea which neurons are involved in speech. Our main finding is that these three mutations in NAGPA in people with persistent stuttering all have harmful effects. This is biochemical evidence that these mutations are meaningful and not just markers of some other genetic change that is the real cause."

Even worse news, these mutations account for only ten percent of stutterers whose families have a history of stuttering. That leaves the majority of stutterers still waiting for answers.