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Researchers find gene for rare disorder that paralyzes children's legs

Childhood form of hereditary spastic paraplegia stems from mutated gene for key nerve cell protein

ANN ARBOR, MI - Scientists report today that they have found a gene for a rare leg-weakening nerve disease that slowly robs children of their ability to walk - a finding that opens the door to better diagnosis and treatment of the disorder, and to insights into other spinal cord problems.

Led by researchers from the University of Michigan Health System who have focused for years on both the childhood and adult forms of the mysterious group of disorders known as hereditary spastic paraplegia, the team publishes its results in the November issue of Nature Genetics.

"This is a major step forward in our understanding of HSP's causes, and has already allowed us to provide diagnostic testing to a few patients," says U-M neurologist and senior author John K. Fink, M.D. "We've been looking for HSP genes since 1993, and we're happy to have found, at last, the first one for a childhood form of the disease. Now, the search continues for the rest."

Mutations in the gene SPG3A, causing alterations in the newfound protein dubbed "atlastin" that it encodes, may be responsible for as many as 25 percent of childhood HSP cases, says Fink. Together with a test for spastin - a gene for an adult form of HSP found by a French team in 1999 - gene testing may lead to diagnosis for more than 50 percent of HSP.

An estimated 10,000 to 20,000 Americans currently have HSP, though the difficulty in diagnosing the disorders, and the lack of HSP clinics like the one Fink leads at UMHS, may mean there are more "hidden" cases misdiagnosed as familial cerebral palsy, primary lateral sclerosis, multiple sclerosis and even vitamin deficiencies.

The disease is insidious, and may begin as toe-walking in early childhood; or subtle difficulty walking and occasional stumbling. But as nerves within the spinal cord break down, HSP can progress to a c
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Contact: Kara Gavin
umhsmedia@umich.edu
734-764-2220
University of Michigan Health System
28-Oct-2001


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