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Mutations in the Glucocerebrosidase Gene and Parkinson's Disease in Ashkenazi Jews Judith Aharon-Peretz, M.D., Hanna Rosenbaum, M.D., and Ruth Gershoni- Baruch, M.D. The New England Journal of Medicine Volume 351:1972-1977 November 4, 2004 Number 19 ABSTRACT Background A clinical association has been reported between type 1 Gaucher's disease, which is caused by a glucocerebrosidase deficiency owing to mutations in the glucocerebrosidase gene (GBA), and parkinsonism. We examined whether mutations in the GBA gene are relevant to idiopathic Parkinson's disease. Methods A clinic-based case series of 99 Ashkenazi patients with idiopathic Parkinson's disease, 74 Ashkenazi patients with Alzheimer's disease, and 1543 healthy Ashkenazi Jews who underwent testing to identify heterozygosity for certain recessive diseases were screened for the six GBA mutations (N370S, L444P, 84GG, IVS+1, V394L, and R496H) that are most common among Ashkenazi Jews. Results Thirty-one patients with Parkinson's disease (31.3 percent; 95 percent confidence interval, 22.2 to 40.4 percent) had one or two mutant GBA alleles: 23 were heterozygous for N370S, 4 were heterozygous for 84GG, 3 were homozygous for N370S, and 1 was heterozygous for R496H. Among the 74 patients with Alzheimer's disease, 3 were identified as carriers of Gaucher's disease (4.1 percent; 95 percent confidence interval, 0.0 to 8.5 percent): 2 were heterozygous for N370S, and 1 was heterozygous for 84GG. Ninety-five carriers of Gaucher's disease were identified among the 1543 control subjects (6.2 percent; 95 percent confidence interval, 5.0 to 7.4 percent): 92 were heterozygous for N370S, and 3 were heterozygous for 84GG. Patients with Parkinson's disease had significantly greater odds of being carriers of Gaucher's disease than did patients with Alzheimer's disease (odds ratio, 10.8; 95 percent confidence interval, 3.0 to 46.6; P<0.001) or control subjects (odds ratio, 7.0; 95 percent confidence interval, 4.2 to 11.4; P<0.001). Among the patients with Parkinson's disease, patients who were carriers of Gaucher's disease were younger than those who were not carriers (mean [±SD] age at onset, 60.0±14.2 years vs. 64.2±11.7 years; P=0.04). Conclusions Our results suggest that heterozygosity for a GBA mutation may predispose Ashkenazi Jews to Parkinson's disease. Source Information From the Department of Neurology and the Cognitive Neurology Unit (J.A.-P.) and the Departments of Hematology and Bone Marrow Transplantation (H.R.) and Human Genetics (R.G.-B.), Rambam Medical Center; and the Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology (J.A.-P., H.R., R.G.-B.) — both in Haifa, Israel. Address reprint requests to Dr. Gershoni-Baruch at the Department of Medical Genetics, Rambam Medical Center, Haifa 31096, Israel, or at [log in to unmask] Full Text of this Article http://content.nejm.org/cgi/content/full/351/19/1972 SOURCE: The New England Journal of Medicine http://tinyurl.com/53rcb * * *Murray Charters <[log in to unmask]> Please place this address in your address book Please purge all others Web site: Parkinsons Resources on the WWWeb http://www.geocities.com/murraycharters ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn