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Last Updated: Nov 17th, 2006 - 22:35:04

Parkinson's Channel
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Latest Research : Aging : Parkinson's

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Most common genetic cause of Parkinson's disease identified
Feb 16, 2005, 19:29, Reviewed by: Dr.



 
Two new studies strongly suggest that a mutation in a recently discovered gene is the most common genetic cause of Parkinson's disease identified to date. The discovery by an international research team provides fresh evidence that genetics may contribute to the development of some cases of Parkinson's disease. The findings could lead to the development of a genetic test to detect the mutation in individuals at risk. The research team includes investigators at the National Institute on Aging (NIA) and scientists supported by the National Institute of Neurological Disorders and Stroke (NINDS).

Parkinson's disease, which affects at least 500,000 Americans, is a progressive neurologic disorder that is caused by the degeneration of nerve cells in the portion of the brain that controls movement. Scientists have long suspected genetics plays a role in the onset of the disease. In these studies, the investigators found that a mutation in the gene LRRK2 appears to occur in at least one of every 60 people who have the disease. Overall, the mutation could be responsible for up to 5 percent of Parkinson's disease in people with a family history of the disorder and may account for 1� to 2 percent of cases in individuals who do not have a family history of the disease. The researchers found a mutation in one copy of the gene can lead to the disease. The findings were published online by Lancet at 6:30 p.m. ET on January 17, 2004.

"Among the forms of Parkinson's disease that are genetic in origin, this gene mutation causes more cases of Parkinson's disease than any other gene discovered to date," says Andrew Singleton, Ph.D., chief of the Molecular Genetics Unit in the NIA's Laboratory of Neurogenetics. "Knowing that this mutation is not only important in familial forms of disease, but in typical sporadic disease, where there is no strong family history, could lead to earlier detection of Parkinson's disease. Further study of how this gene works also might help scientists identify new treatments."

In addition to Dr. Singleton, the collaborative work was spearheaded by William C. Nichols, Ph.D., of Cincinnati Children's Hospital, Tatiana Foroud, Ph.D., of Indiana University Medical Center, Indianapolis, and Nicholas W. Wood, M.D., of the Institute of Neurology in London. The NIA and the NINDS are part of the National Institutes of Health (NIH) at the U.S. Department of Health and Human Services.

Singleton and his colleagues recently discovered LRRK2, a gene that encodes a protein named dardarin by the researchers from the Basque word dardara, which means tremor, a major symptom of Parkinson's disease. It was isolated on a region of chromosome 12 called PARK8 by investigators who studied five families with a history of Parkinson's disease who lived in the Basque region of Spain and in England.

In these new studies, the researchers sought to determine the prevalence of the genetic mutation in other families and individuals being studied by the Parkinson's Study Group with NINDS support. In an analysis of 358 families with a history of Parkinson's disease, for instance, the investigators found that 34 of the 767 people who had inherited the disease had at least one copy of the mutated gene. Similarly, the team detected one copy of the mutation in 8 of 482 people with Parkinson's disease, but who didn't report a family history of the disease. The Parkinson's Study Group is a non-profit, cooperative group of Parkinson's disease experts from 59 medical centers in the United States and Canada who are dedicated to improving treatment for people affected by Parkinson's disease.

"NINDS is pleased to have supported the collection of this large group of families and sibling pairs, which is proving to be an invaluable resource for these studies," says Diane Murphy, Ph.D., a program director at NINDS. "Because the prevalence of this mutation is 5 percent in families with a history of the disease and it is relatively common even among those without a family history, it's possible that detecting this mutation will help identify people at increased risk for Parkinson's disease."

About 50,000 Americans are diagnosed with Parkinson's disease each year. The disease occurs when certain nerve cells die or become impaired and can no longer produce dopamine, a brain signaling chemical (neurotransmitter). Without it, individuals can develop tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability or impaired balance and coordination. Patients may also have difficulty walking, talking, or completing other simple tasks. The disease is both chronic and progressive. Incidence of the disease increases with age, with an average onset at about 60 years.
 

- The findings were published online by Lancet at 6:30 p.m. ET on January 17, 2004.
 

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The NIA conducts and supports research on aging and age-related diseases, including neurodegenerative diseases such as Parkinson's disease. For more information on NIA's research programs in this area, visit its Alzheimer's Disease Education and Referral (ADEAR) Center website at www.alzheimers.org , or call 1-800-438-4380. The National Institute of Neurological Disorders and Stroke (NINDS), also part of the NIH, conducts research on Parkinson's disease and other neurological disorders and provides information to the public and to patients on the disease.

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