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Genetic Link to Parkinson's Disease Is Detected in 2 Ethnic Groups

Scientists say a mutation causes 18% of cases in Ashkenazi Jews and 37% in North African Arabs.

January 26, 2006|Thomas H. Maugh II | Times Staff Writer

A recently discovered mutant gene causes 18% of Parkinson's disease cases in Ashkenazi Jews and 37% in North African Arabs -- a surprising finding because genetics had been thought to play only a small role in the disorder.

The discovery will allow genetic counseling and early diagnosis of the disease in the affected groups, said Dr. Susan B. Bressman, a neurologist at the Albert Einstein College of Medicine in New York and the leader of one of two studies on the subject published today in the New England Journal of Medicine.

Although there is no known way to prevent development of the brain disorder, which affects at least half a million Americans, early diagnosis would allow expanded use of newer drugs that delay its onset.

The fact that the gene plays such a large role in the two ethnic groups suggests that other mutated genes -- perhaps different variants of this one -- cause the disease in other ethnic groups.

The mutant form of the gene LRRK2 was linked to Parkinson's in late 2004 by two groups, a joint U.S.-Spanish team and one at the University of Tubingen in Germany.

It was identified in members of a large family in the Basque region of Spain, and the protein it produces was given the name Dardarin, Basque for "tremor."

It was the third gene linked to the disorder. The two other genes produce unusual forms of Parkinson's disease that have an earlier onset and a more aggressive course.

LRRK2 produces symptoms very similar to those observed in the majority of Parkinson's patients, although it is found in only 2% to 3% of people with the disease.

Bressman and her colleagues studied DNA from 120 Ashkenazi Jews with Parkinson's disease and 317 healthy Ashkenazi Jews. Ashkenazim, or Jews of Eastern European descent, account for an estimated 80% of Jews worldwide.

The researchers found that 18% of those with Parkinson's carried the specific mutation, compared with about 1% of the healthy subjects -- meaning that the presence of the gene in Ashkenazim increased the risk of developing Parkinson's 15 to 20 times. Among patients with a family history of the disorder, 30% carried the mutant gene.

In a similar study led by Dr. Alexis Brice and geneticist Suzanne Lesage of the French research institute INSERM, the team found that about 30% of North Africans with Parkinson's carried the specific mutation, compared with 3% of the healthy subjects. Among North African Arabs with the disease, the incidence of the gene rose to 37%.

"The importance of genetics [in Parkinson's disease] has been disputed for years and years," Bressman said. Most people thought it was primarily environmental in origin, perhaps from pesticides or some other toxin.

Now, in at least two ethnic groups, genetics "is very important," she said.

Dr. Neil Risch of UC San Francisco, who participated in Bressman's study, said the mutation probably arose in a common ancestor of the Jews and Arabs several thousand years ago. The mutation, he added, is probably important in multiple Middle Eastern populations.

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