Two copies of G2019S Parkinson's gene mutation doesn't lead to more severe disease

A group of Parkinson's disease researchers concluded there are no observable differences between those who have two copies of the most common mutation of the recently discovered LRRK2 gene and those who have only one copy. Their study will be published in the September edition of the Archives of Neurology.

In most diseases with a genetic cause or component, two copies of a bad gene lead to more severe visible manifestation of the disease. Researchers expected to see worse symptoms, the disease start earlier in life and a shorter life span for those with two copies of the LRRK2 gene with the G2019S mutation. "That proved not to be the case," says Mayo Clinic neurologist Zbigniew Wszolek, M.D.

Wszolek formed an international consortium that compared the clinical features of Parkinson's disease in the two groups. "It's puzzling," he says. "More studies are needed. More patients need to be identified and, hopefully, more basic science research is going to be performed to find out why."

The G2019S mutation is the most common of the 20 identified LRRK2 diseasecausing mutations. There are six known genes that cause familial Parkinson's disease, but only one, the G2019S mutation of the LRRK2 gene, has been associated with previously unexplained cases of Parkinson's disease. Wszolek and his colleagues hope that studying the ways in which these genes cause disease, especially the G2019S mutation, will lead to improved treatments and even a cure. "We are all united by the common drive to learn more about this disease, to help the people with this illness and to bring us closer to curative treatments," Wszolek says. "And this may be a step in that direction."

By pooling their studies from around the globe, Wszolek and his colleagues found 26 people with the G2019S mutation in both copies of their LRRK2 gene--one inherited from the mother and the other from the father. Interestingly, three patients with the dual mutation exhibited no c

Contact: Erik Kaldor
Mayo Clinic, Jacksonville

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