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NIH Research Matters

October 26, 2009

Rare Disease Gene Linked to Parkinson’s Disease

People with mutant forms of the gene that causes the rare disorder Gaucher disease are 5 times more likely to develop Parkinson's disease than the general public, according to a new study. The finding may lead to new insights into developing novel therapeutic strategies for these disorders.

Photo of engorged cells.

In Gaucher disease, a faulty GBA gene causes fatty molecules to accumulate and engorge cells. New research also links GBA mutations to Parkinsonís disease. Image courtesy of Wellcome Photo, all rights reserved by Wellcome Images.

Parkinson's disease is a neurodegenerative disorder that affects about 1.5 million Americans. The likelihood of developing the disorder increases with age and involves a combination of environmental risk factors and genetic susceptibility.

Earlier research by scientists at NIH's National Human Genome Research Institute (NHGRI) and elsewhere found evidence that people with alterations in the GBA gene, which is responsible for Gaucher disease, may also be at increased risk for Parkinson's disease. But the studies weren't large enough to make a definitive link.

Gaucher disease arises when people inherit 2 defective copies of the GBA gene, which codes for the enzyme glucocerebrosidase. When defective, the enzyme can't perform its normal duty of breaking down fatty molecules for disposal. The fatty molecules build up and engorge cells. Ultimately, this buildup can damage the spleen, liver, lungs, bone marrow and, in some cases, the brain.

To clarify the relationship between GBA and Parkinson's disease, scientists from 16 research centers around the world pooled their genetic data on 5,691 Parkinson's patients. The patients included 780 Ashkenazi Jews, a population in which a particular type of Gaucher disease is more prevalent. These data were matched against a control group of 4,898 unaffected volunteers, including 387 Ashkenazi Jews. Dr. Ellen Sidransky, senior investigator in NHGRI's Medical Genetics Branch, is the lead author of the study and coordinated the effort. The research was supported in part by NHGRI and several other NIH components.

In the October 22, 2009, issue of the New England Journal of Medicine, the scientists reported that more than 3% of the Parkinson's patients—but only 0.6% of controls—had at least 1 of 2 common GBA alterations. Among Ashkenazi subjects, 15.3% of those with Parkinson's disease carried one of these GBA alterations compared to 3.4% of controls.

In addition to screening for the 2 common alterations, the entire GBA gene was sequenced in a subset of non-Ashkenazi volunteers—1,883 with Parkinson's disease and 1,611 controls. This more thorough analysis linked several more mutations to Parkinson's disease. Overall, 7% of the Parkinson's patients were found to have the GBA alterations. Those Parkinson's patients with the GBA alterations also had an earlier disease onset.

“This analysis illustrates how studying a rare but important disorder, like Gaucher disease, can provide powerful clues about more common disorders, such as Parkinson's disease,” said NHGRI Scientific Director Dr. Eric Green. “Understanding the genetic basis of rare conditions can thus provide insights into normal cellular and biological processes, which in turn may lead to improved diagnostic and therapeutic strategies.”

These mutations are among the most significant risk factors found to date for Parkinson's disease. However, many GBA mutation carriers, as well as patients with Gaucher disease, never develop Parkinson's disease. Other risk factors are clearly involved in the development of the disease.

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Editor: Harrison Wein, Ph.D.
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NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on December 4, 2012

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