A large proportion of Ashkenazi Jews and North African Arabs with Parkinson’s disease carry the same single gene mutation

Michael Smith:

The mutation -- apparently derived from a single “founder” individual several centuries ago -- was found in 18.3% of a cohort of 120 Ashkenazi Jews treated for Parkinson’s at the Albert Einstein College of Medicine and Beth Israel Medical Center here.

The same mutation was found in 39% of a cohort of 76 Arabs with the disease, French researcher said. Both studies were published as letters in the Jan. 26 issue of the New England Journal of Medicine.

The single-base-pair alteration, dubbed G2019S, is found on exon 41 of the leucine-rich repeat kinase 2 (LRRK2), according to Laurie Ozelius, Ph.D., of the Albert Einstein College of Medicine and lead author of the paper describing the Jewish cohort.

Overall, Dr. Ozelius said, 22 of the 120 Parkinson’s patients carried the mutation, but only four of 317 controls with the same ethnic background carried the mutation. Carrying the mutation gave an odds ratio for disease of 17.6, with a 95% confidence interval ranging from 5.9 to 52.2.

Also, the mutation was found in 11 of 37 (29.7%) of patients with a familial pattern of disease, and 11 of 83 (13.3%) patients with apparently sporadic disease.

One implication of the finding, Dr. Ozelius said in an interview, is that many patients thought of as having sporadic disease probably have familial -- but unknown or unrecognized -- connections.

“What this is telling us is that there is this group of people who supposedly have sporadic Parkinson’s, but actually have a genetic form of the disease,” she said.

The gene mutation has been shown to be due to a single founder in European populations, where it is carried by about 5% of familial patients and 1% of sporadic patients -- rates much lower than those found by the New York group, Dr. Ozelius said.

However, genetic markers in and surrounding the altered gene in the Jewish cohort show that it is identical to the gene found in the European studies. “The mutation is the same mutation as that in the European population – it’s due to the same founder,” Dr. Ozelius said.

The New York results, combined with the Arab study, which also found the same genetic pattern, imply that the gene mutation has its origins in the Middle East. Dr. Ozelius said some of her colleagues are now trying to estimate when it first appeared.

In the other study, researchers from the French Parkinson’s Disease Study Group examined a cohort of 104 Parkinson’s patients in North Africa, including 76 Arabs, 18 Europeans born in North Africa, six Sephardic Jews, and four black Africans, as well as a cohort of 151 healthy Arab controls.

The study showed that 31 of the 104 patients (30%) carried the mutation, according to Suzanne Lesage, Ph.D., of the French national institute for health and medical research’s unit 679 in Paris, and lead author of the study.

But all but one of the carriers was Arab, Dr. Lesage and colleagues found, and the other carrier was a Sephardic Jew.

Among the 76 Arab patients, the researchers found, 10 of the 27 familial cases (37%) carried the mutation and 20 of the 49 sporadic cases (41%) carried the mutation. Two of the controls were also found to have the mutation. Carrying the mutation gave an odds ratio for disease of 48.6 (95% CI 11.2 to 211) in Arab patients.

Both groups of researchers noted that the finding will have implications for genetic testing and counseling, although the issue is fraught with difficulty since there is no cure for the disease.

But Dr. Ozelius said the findings may also make it possible to tease out some of the earliest signs of Parkinson’s disease, because genetic screening would find carriers of the mutated gene long before they develop symptoms.

“This really opens up our ability to look at a homogenous population -- everyone with the same mutation -- and look at pre-clinical things,” she said.

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