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Mutations in a multifunctional protein cause parkinsonism

A team of researchers at Mayo Clinic in Jacksonville, Fla., and colleagues in Canada and Germany have discovered a gene and six mutations of it that cause symptoms associated with Parkinson's disease and other neurodegenerative disorders. Their discovery will be reported in the Nov. 18 issue of the journal, Neuron.

The team found a mutation of the gene, named LRRK2, in members of six families with many individuals affected by Parkinson's disease. Surprisingly, brain autopsy on deceased, affected family members who participated in this research indicate mutations in the LRRK2 gene play a central role in developing pathology characteristic of Parkinson's disease and other neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease).

For 14 years Mayo Clinic neurologist Dr. Zbigniew Wszolek has studied the two largest families in which a LRRK2 mutation was found. "The discovery of this gene will have major implications for the understanding of mechanisms leading to the development of these neurodegenerative diseases," he says. "We also hope that continued study of this gene will lead to curative treatments for Parkinson's disease and other similar conditions."

Mayo Clinic neurologist Dr. Ryan Uitti has treated members of one of the six families with the gene mutation. "This finding is potentially a giant leap forward," he says. "Many people with Parkinson's disease have dementia as well, and this may help to explain how that occurs."

The discovery is the culmination of research into the cause of autosomal dominant, late- onset Parkinson's disease in the studied families. This team and others have previously narrowed a genetic cause for this form of inherited parkinsonism to a region of chromosome 12 called PARK8.

Mayo Clinic neuroscientist Matthew Farrer, Ph.D., and his team, continued to perform sophisticated genetic analyses on DNA collected from family members
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Contact: Erik Kaldor
kaldor.erik@mayo.edu
904-953-2299
Mayo Clinic, Jacksonville
17-Nov-2004


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