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Different mutations in single gene suggest Parkinson's is primarily an inherited genetic disorder
Date:4/16/2008

led sporadic form. In 2004, they were part of a team that discovered that the LRRK2 gene is linked to both familial and non-familial cases of the disease.

Since then, they have found LRRK2 mutations that can cause the same clinical manifestations of Parkinsons disease in people with and without a family history discoveries that have caused a paradigm shift in the field, says Dr. Ross. For example, a mutation labeled G2019S causes both familial and non-familial Parkinsons disease in a high number of Berber Arabs and Ashkenazi Jews. This shows that the effect of mutations in different areas of the Lrrk2 protein lead to the same disease, although it may not manifest in each generation and so did not appear to be familial, he says.

In the latest study, Dr Ross and colleagues studied 1079 ethnic Han Chinese diagnosed with Parkinsons disease, of which 44 reported a family history of the disease. These patients were compared with 907 ethnically matched Han Chinese who did not have Parkinsons disease, and results showed the R1628P variant was approximately twice as frequent in Parkinsons disease patients as in the control population. From this, the researchers estimated that for every 100 Chinese, 3 will have the gene variant. Further research then suggested that the R1628P carriers were related to a single common founder that dated from about 2,500 years ago.

The researchers then searched for evidence of the mutation in Japanese patients and controls but did not find it. The theory is that this mutation arose in China after the Japanese and Chinese segregated their populations, which explains why the G2385R mutation, which is 2,000 years older than R1628P, is found in both populations and is more common, Dr. Ross says.

Inheriting one or both of these mutations doesnt mean that a person will develop Parkinsons disease, but that an individuals risk is increased, he says. The basis of population genetics is that disease is familial; pe
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Contact: Cynthia Nelson
nelson.cynthia1@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

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