These days, as delegates to the AAAS meeting in Washington, DC, heard, the talk is of brain anatomy and genes. Luc De Nil, of the University of Toronto, has been poring over stutterers’ brains using positron emission tomography and functional magnetic resonance imaging. He has found that parts of the brain linked to the production of speech are more active in stutterers than non-stutterers, while those involved in perceiving sounds are less so. The two sorts of brain look different, too. Stutterers tend, for instance, to have more densely packed grey matter in the areas associated with processing and producing sounds. Such differences in activity and anatomy, though, must have deeper causes. And, in time-honoured fashion, there is a debate about whether those causes are genetic or environmental.
Dennis Drayna of America’s National Institutes of Health argued to the meeting that persistent stuttering is at least partly a matter of genes. It runs in families. Studies of twins suggest a genetic component larger than those known to be involved in high cholesterol and osteoporosis. At least two studies of adopted children suggest that those whose adoptive parents stutter are no more likely to develop the impediment than those taken on by non-stutterers.
To discover which genes might be responsible, Dr Drayna looked at 44 Pakistani families. Marriage between cousins is common in Pakistan, and such inbreeding leads to a high incidence of genetic disorders. Dr Drayna’s analysis suggests that stuttering is linked to mutation of a gene called GNPTAB—a finding confirmed when the same mutation was subsequently discovered in a number of stutterers from Pakistan and India who were unrelated to the original group of families. In January Dr Drayna and his colleagues published a paper in the Journal of Human Genetics tracing the responsible mutation back almost 600 generations, to a common ancestor who would have lived around 14,000 years ago.
Further study of South Asians has shown that mutations in two other genes, GNPTG and NAGPA, are found in individuals who stutter, but not in non-stutterers. All three affected genes encode enzymes that regulate lysosomes, the cell’s waste-disposal units. Two of the mutations involved are also known to cause a rare disease called mucolipidosis. Severe mucolipidosis is fatal within ten years of birth. Even the mild variety has symptoms that include abnormal skeletal development and, sometimes, slight mental retardation.
Fortunately for stutterers, close examination of those with the relevant mutations reveals no symptoms of mucolipidosis. Dr Drayna suspects that both conditions are caused by misfolding of the enzymes in question, but that the details are different. With stutterers, he thinks, a specific group of brain cells involved in speech production is, for an unknown reason, uniquely sensitive to the enzymatic glitch—perhaps producing the patterns seen by Dr De Nil in his brain scanners.
To investigate further, Dr Drayna is now attempting to splice human stutter-causing genes into the DNA of mice. That, of course, raises the question of what a stuttering mouse sounds like. To the human ear, it may not sound like anything. Many murine squeakings are too high-pitched to be perceptible. But ultrasonic detectors should deal with that. With luck, the causes of stuttering should soon be understood better. Whether that results in treatments more effective than lettuce juice and wine is another matter.
LINK: The Economist http://www.economist.com/node/18226793
