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Scientists Link Fatal, Cholesterol-Storage Disorder to Chromosome 18


For release: Monday, March 1, 1993

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) have linked a deadly brain disorder, called Niemann-Pick Type C disease, to a small region of human chromosome 18. These findings, reported in the current issue of Proceedings of the National Academy of Sciences ,* may eventually lead to improved diagnosis and treatment for this inherited disorder and yield new insight into the metabolism of cholesterol inside the body's cells.

"These findings represent a critical step forward in identifying the faulty gene that causes Niemann-Pick Type C disease. Once that is accomplished, we will be poised to develop specific, effective treatment for this devastating disorder," said Roscoe Brady, M.D., chief of the NINDS Developmental and Metabolic Neurology Branch.

About 200 to 300 Americans have Niemann-Pick Type C disease, in which faulty metabolism of cholesterol within cells leads to abnormal cholesterol buildup in the brain, liver, and spleen. Affected children typically develop normally until school age, then begin to regress. The first symptoms of the disease can be subtle, such as declining performance in school, but as the disease progresses, brain damage worsens, causing progressive dementia and motor problems, including difficulty with walking, talking, and swallowing. Most patients die before they reach the age of 20.

"I have high hopes that identifying the disease gene for Niemann-Pick Type C will help us learn more about how cholesterol is processed inside cells of the brain and other organs," said Peter G. Pentchev, Ph.D., an NINDS biochemist who has been conducting Niemann-Pick Type C research for more than a decade. "This information, in turn, could offer vital insights into how this process goes awry not only in this disorder, but also in such common killers as heart disease and stroke."

In the current study, a collaborative team of scientists** analyzed DNA samples from 12 affected families and identified a small region on chromosome 18 most likely to house the recessive disease gene. "We've drastically reduced the size of the hunt for this gene. The region we've identified covers less than 3 percent of chromosome 18, and, with a little luck, we should identify the precise gene soon," Dr. Pentchev said.

Scientists will then be ready to determine the corresponding protein defect and to devise new treatments, including drugs designed to intervene in the disease process and protein or gene replacement therapy, Dr. Brady added.

The NINDS, one of the 16 National Institutes of Health located in Bethesda, MD, is the nation's leading supporter of research on disorders of the brain and nervous system and a lead agency, along with the National Institute of Mental Health, for the congressionally mandated Decade of the Brain.

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* Carstea, E. et. al. "Linkage of Niemann-Pick Disease Type C to human chromosome 18," Proceedings of the National Academy of Science, March 1, 1993, pp. 2002-2004.

**Authors for the current paper are:

NINDS: Eugene D. Carstea, Colette C. Parker, Raymond R. O'Neill, Marc C. Patterson, Ehud Goldin, Roscoe O. Brady, and Peter G. Pentchev. National Institute of Mental Health: Michael H. Polymeropoulos, Sevilla D. Detera-Wadleigh, and Hong Xiao. Columbia University: Richard E. Straub. Lyon-Sud School of Medicine, France: Marie T. Vanier

Last Modified August 7, 2009