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Scientists Isolate "Crown Jewel" — Huntington's Disease Gene

For release: Tuesday, March 23, 1993

Scientists have identified the genetic mutation that causes Huntington's disease (HD), a fatal, neurodegenerative disorder characterized by progressive physical and mental deterioration. The discovery, to be reported in the March 26 issue of Cell ,* is the culmination of a 10-year-long collaboration between investigators in six laboratory groups around the world with major support from the National Institute of Neurological Disorders and Stroke (NINDS).

"The Huntington's gene may prove to be the crown jewel of recent neurogenetic discoveries," said NINDS Director Murray Goldstein, D.O., M.P.H. "The relentless dedication of these skilled investigators is unparalleled. Their search for the Huntington's gene has given us enormous information about genetic mutations and the methods we employ to find them. Now these scientists have given us the key to a definitive diagnostic test."

About 25,000 people have Huntington's disease and at least 100,000 others are at risk for developing the disorder. It usually strikes people between the ages of 35 and 45, although symptoms can develop in those younger than 20 or older than 60.

In the study, over 50 investigators from nine different institutions, working together as The Huntington's Disease Collaborative Research Group, isolated an expandable, unstable DNA segment on chromosome 4 that can change from generation to generation and even among affected siblings. The genetic mutation is a multiple repeat phenomenon similar to the defects responsible for fragile-X syndrome, myotonic dystrophy, and spino-bulbar muscular atrophy. The immediate effect of the discovery will be to improve the accuracy of diagnostic testing, and scientists expect that such a test will become available almost immediately.

"For a number of years, the Institute has supported studies to advance the search for the gene that causes HD," said Carl M. Leventhal, M.D., director of the NINDS program that supported much of the research. "We are already able to see the gene's effect on the structures of the brain that are affected as the disease progresses, the gene's effect on individual nerve cells, and we have been learning which brain chemicals may play a role in HD. Now that we have the gene, we hope to put these clues together and discover how the disease causes progressive neurological and behavioral deterioration."

Scientists began looking for the gene in response to a set of recommendations issued in 1977 by the congressionally mandated Commission for the Control of Huntington's Disease and Its Consequences. The group was chaired by Marjorie Guthrie, the late widow of singer/composer Woody Guthrie who died in 1967 of the disease.

In 1983, NINDS-supported investigators discovered the first genetic marker for HD, identifying chromosome 4 as the site of the gene. This discovery accelerated the search for the gene, but its precise location continued to elude investigators until now.

In the hunt for the gene, the investigators used an NINDS-supported national research roster of patient information at Indiana University at Indianapolis, a brain bank at McLean Hospital near Boston, and yearly studies of the largest kindred of HD patients living near Lake Maracaibo, Venezuela. Nancy S. Wexler, Ph.D., of the Santa Monica-based Hereditary Disease Foundation conducted the Venezuelan studies and played an integral role in organizing the collaborative effort. In addition, NINDS-supported grantees at the Huntington's Disease Center at the Massachusetts General Hospital in Boston and the University of California, Irvine figured prominently in the research.

"We've been expecting a number of explosive scientific discoveries during the Decade of the Brain," said Dr. Goldstein. "The HD gene is the third gene for a neurological disorder to be isolated by Institute-supported scientists this month alone, and the discovery of the HD gene is especially exciting because it has eluded us for so long." The other genes isolated were for the familial form of ALS (Lou Gehrig's disease) and neurofibromatosis type 2. Also in March, NINDS scientists linked a deadly brain disorder, called Niemann-Pick Type C disease, to a small region of human chromosome 18.

The NINDS, one of the National Institutes of Health located in Bethesda, Md., is the nation's largest supporter of research on the brain and nervous system and a lead agency for the congressionally designated Decade of the Brain. The Institute conducts and supports a broad program of basic and clinical neurological investigations into HD at leading biomedical research institutions.

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* The Huntington's Disease Collaborative Research Group, "A Novel Gene Containing a Trinucleotide Repeat That is Expanded and Unstable on Huntington's Disease Chromosomes," Cell, March 26, 1993, pp. 1-20.

Last Modified September 23, 2013