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Valerie Street was a 20-year-old college student when a neurologist in her lab class demonstrated a nerve conduction test. Street offered to be the subject and was surprised to learn that she might have an inherited neurological disorder called Charcot-Marie-Tooth. This slowly progressive disease damages the peripheral nerves and can cause weakness and wasting of muscles in the hands, forearms, lower legs, and feet.
As a tri-athlete with no symptoms, Street didn't give the test results much thought. However, nine years later, when she began to feel severe foot pain, she remembered the lab demonstration and contacted Dr. Thomas Bird at the UW Department of Neurology, an expert on Charcot-Marie-Tooth. Bird forwarded Street's lab work to Dr. Phillip Chance, another authority on the disease who specializes in genetics and neurology.
That is how Street and Chance began collaborative work on this genetic disorder. At age 15, Chance had put aside his pursuit of a career as a professional musician when he, like Street, learned he had Charcot-Marie-Tooth
Today, Chance is professor of pediatrics and neurology at the UW School of Medicine and chief of the Division of Genetics and Developmental Medicine at Children's Hospital and Regional Medical Center. Street is an acting instructor in Otolaryngology-Head and Neck Surgery Department at the Virginia Merrill Bloedel Hearing Research Center, and an associate of the Center on Human Development and Disability.
Chance and Street use gene mapping and molecular cloning to understand the molecular and biochemical abnormalities of Charcot-Marie-Tooth.
Approximately 25 different forms of Charcot-Marie-Tooth have been mapped to specific regions in the genome. For about half of these forms, the abnormal gene has been found.
In their recent work, the UW team studied Charcot-Marie-Tooth 1C, a form of the disease for which no associated gene or chromosomal defect had been identified. They mapped the abnormal gene to chromosome 16 using blood samples Bird collected from two Northwest families diagnosed with Charcot-Marie-Tooth 1C in four or more generations. The researchers found mutations in a gene called SIMPLE (small integrated membrane proteins of the lysosome/late endosome), which codes for a protein critical for normal peripheral nerve function.
Approximately 150,000 people in the United States have Charcot-Marie-Tooth, but not all have severe symptoms or are diagnosed correctly. There are no effective treatments.
Street's and Chance's own experience with Charcot-Marie-Tooth personalizes their approach in working to help others.
"For me, genetic disease is not just about DNA in a test tube," Street said. "Those DNAs are from people trying to deal with their disease every day."
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