Researchers funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) have identified the gene that causes a rare juvenile-onset form of amyotrophic lateral sclerosis (ALS).
The discovery of the Senataxin gene, on chromosome 9q34, may provide clues to the mechanisms of related brain disorders. The study appears in the June 2004 issue of the American Journal of Human Genetics.
ALS is a progressive disorder that destroys motor neurons, the cells that control voluntary muscle activity such as speaking, walking, and writing. Affected muscles gradually weaken and waste away, and patients eventually are unable to move voluntarily. About 10% of all cases of ALS are inherited.
Mutations in the Senataxin gene cause ALS4, a juvenile-onset form that usually begins before age 25. These mutations likely lead to a protein that has harmful cellular effects. Unlike classical ALS, which is a fatal disease, ALS4 causes weakness that is slowly progressive, and affected individuals typically have a normal life span. Sensation in ALS4 is not altered.
A team of researchers led by Phillip F. Chance, M.D, a professor of pediatrics and neurology at the University of Washington, Seattle, studied four unrelated families (from the US, Belgium, Austria, and England), each of whom had multiple family members affected by a childhood- or adolescent-onset, slowly progressive motor neuron disorder with minimal or no sensory nerve impairment. Electrophysiological studies and autopsies confirmed the diagnosis of a chronic motor nerve disorder that initially affected distal muscles (those farthest away from the center of the body). Further analysis revealed an alteration in the DNA sequence of the Senataxin gene on chromosome 9 in the US family. The scientists then studied DNA samples from the other three families, and similar mutations were found in two additional families.
Although the exact function of the Senataxin gene is unknown, scientists believe that the mutated protein may disrupt normal mechanisms through which cells rid themselves of defective RNA transcripts.