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LRRK2 gene mutation as major cause of Parkinson's in Ashkenazi Jewish patients

Researchers at the Albert Einstein College of Medicine of Yeshiva University and Beth Israel Medical Center, have found that a specific mutation in a single gene is a major cause of Parkinson's disease among Ashkenazi ( Eastern European ) Jews.

The study is published in the The New England Journal of Medicine.

" Like the discovery of the BRCA1 and BRCA2 gene mutations for breast cancer, this finding will directly affect the way Parkinson's disease is diagnosed in Ashkenazi Jews," says Susan B. Bressman, senior investigator of the report, at Beth Israel and at Einstein. " It also emphasizes the benefit of focusing genetic studies in a specific ethnic group, even with regard to a disease not thought to be primarily genetic in origin,"

" Up until now, genetic counseling for Parkinson's disease hasn't really been considered," adds study co-author Laurie J. Ozelius, at Einstein. " Our finding should bring genetic counseling for Parkinson's disease to the forefront along with genetic testing for early detection of Parkinson's disease."

The researchers focused on a gene called LRRK2, which is mutated in about 1% of late-onset non-familial cases of Parkinson's disease in those patients who are primarily of European ancestry.

Their study involved 120 unrelated Ashkenazi Jewish Parkinson's disease patients who had been seen as outpatients at Beth Israel's neurology department and screened for the gene.

For comparison, a control group of 317 Ashenazi Jews who did not have Parkinson's disease was also studied. DNA was extracted from white blood cells or cheek cells of all the study participants and analyzed for mutations.

The G2019S mutation, the most common of several possible LRRK2 mutations, was detected in 18.3 percent ( 22 out of 120 ) of the Ashkenazi Jewish Parkinson's patients compared with only 1.3 percent ( 4 out of 317 ) of control patients.

The mutation's role was even more dramatic when the 120 Parkinson's disease patients were divided into those ( 37 ) with a family history of the disease ( defined as having at least one affected first, second, or third degree relative ) and those ( 83 ) with no family history.
The G2019S mutation was found in 29.7 percent ( 11/37 ) of the familial Parkinson's cases but also in 13.3 percent ( 11/83 ) of so-called sporadic or nonfamilial cases.
The frequency of this mutation among Ashkenazi Parkinson's patients was 15 to 20 times higher than has been reported among patients of European ancestry in general.

In addition to Ashkenazi Jews, the researchers note that a group of North Africans of Arab descent have been found to have a high frequency of this same gene mutation as a cause of Parkinson's disease. The two groups appear to share the same origin or founder, suggesting a probable Middle Eastern origin for this mutation.

Source: Albert Einstein College of Medicine, 2006