Gene causes Parkinson's in Ashkenazim

Discovery expected to spur genetic counseling for couples, testing in elderly.

January 25, 2006 21:52
2 minute read.
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parkinsons brain 88. (photo credit: )


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Although Parkinson's disease has not generally been regarded as genetic in origin, researchers at Yeshiva University's Einstein College of Medicine and Beth Israel Medical Center in New York have discovered a single gene that is the "major cause" of Parkinson's in Ashkenazi Jews. The report appears as "Correspondence" in the January 26 issue of the prestigious New England Journal of Medicine. The discovery should bring genetic counseling for Parkinson's disease in couples to the forefront. It can also lead to genetic testing of older people for its early detection of the disease, whose progress can be delayed with drugs, said Prof. Susan Bressman, chief of neurology at Beth Israel and also vice-chairman of neurology at the medical school. Parkinson's is an incurable neurological disorder that causes severe disability and eventually death. Bressman headed the research team along with Dr. Lauri Ozelius, an Einstein molecular geneticist. "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," Ozelius added. "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." The researchers focused on a gene called LRRK2 (leucine-rich repeat kinase 2), which is mutated in about one percent of late-onset, non-familial cases of Parkinson's disease in Jewish patients who are primarily of European ancestry. Their study involved 120 unrelated Ashkenazi Jewish Parkinson's 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 mutation, called G2019S, was detected in 18.3% (22 out of 120) of the Ashkenazi Parkinson's patients, compared with only 1.3% (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% (11/37) of the familial Parkinson's cases but also in 13.3% (11/83) of so-called sporadic or non-familial cases. The frequency of this mutation among Ashkenazi Parkinson's patients was 15-20 times higher than has been reported among patients of European ancestry in general. Besides Ashkenazi Jews being identified as carriers, 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. Doron Behar, a doctoral student at the Technion-Israel Institute of Technology - who only recently found with Prof. Karl Skorecki that four "founding mothers" produced 3.5 million living Ashkenazi descendants - commented to The Jerusalem Post that the new study was "very interesting. It seems like Parkinson's is yet another disease that can be inherited via a single genetic defect, of which there are already more than 20." It also shows, he said, that Ashkenazi Jewry began some 1,000 years ago with a few founders, and that their isolation as a community and marriage among themselves amplified the presence of defective genes that cause these diseases.

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