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A Hereditary Ataxia Caused by Huntington's-Type "Genetic Stutter"


For release: Wednesday, June 30, 1993

Scientists have discovered that another nervous system degenerative disorder, spinocerebellar ataxia type 1 (SCA1), has the same type of gene mutation occurring in Huntington's and Kennedy's diseases. Two teams of research scientists funded by the National Institute of Neurological Disorders and Stroke (NINDS) announced their discovery of the "genetic stutter" in this week's Nature Genetics *. In the disease, a normal three-base sequence in the genetic code — cytosine, adenine and guanine, or CAG — is abnormally repeated, according to Drs. Huda Y. Zoghbi, who led one team at the Baylor College of Medicine in Houston, Texas, and Harry T. Orr, who headed the other team at the University of Minnesota in Minneapolis. The same CAG repeat was reported earlier this year in Huntington's disease and in 1991 in the very rare Kennedy's disease, also called X-linked spinobulbar muscular atrophy.

"For the 10,000 or so Americans who have SCA1 and their families, this discovery means that we will soon have a relatively inexpensive test to confirm diagnosis, even though we don't yet have a cure," said NINDS director Dr. Murray Goldstein. "In addition, new techniques to screen for these repeats may be a shortcut to finding genes causing other disorders; the sooner we find a disease-related gene, the sooner we can learn what goes wrong in the cell. There may be common mechanisms of action, and this study provides a clear lead."

In all three disorders, symptoms appear when the repeats exceed about 40. In SCA1 and Huntington's, a larger number of repeats appears to cause symptoms to begin earlier in life and progress more rapidly.

Dr. Zoghbi said she was surprised to find the threshold effect and the high correlation between the number of repeats and the age of onset in SCA1. "Our group is going on to explore the biology of this disease," Dr. Zoghbi said. "We need to understand the exquisite selectivity this CAG mutation has in specific brain cells. In Huntington's one set of cells is destroyed, in SCA1 another, and in Kennedy's a third."

SCA1 is inherited from one parent, and each child of an affected parent has a 50-50 chance of receiving the defective gene. This disease usually begins in early adulthood, but can start in childhood or late adulthood. The symptoms, which include the unsteady walk called ataxia, paralysis of the muscles controlling eye movement, and muscle weakness, gradually worsen leading to disability in 10 to 20 years and eventually death.

The NINDS, one of the National Institutes of Health located in Bethesda, MD, is the nation's leading supporter of research on the brain and nervous system and a lead agency for the Congressionally mandated Decade of the Brain.

*Orr, H.T., et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genetics , Vol. 4, pp. 221-6, July, 1993.

Last Modified August 7, 2009