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Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.
N Engl J Med. 2004 Nov 04; 351(19):1972-7.NEJM

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.

Authors+Show Affiliations

Department of Neurology and the Cognitive Neurology Unit, Rambam Medical Center, Haifa, Israel.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15525722

Citation

Aharon-Peretz, Judith, et al. "Mutations in the Glucocerebrosidase Gene and Parkinson's Disease in Ashkenazi Jews." The New England Journal of Medicine, vol. 351, no. 19, 2004, pp. 1972-7.
Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2004;351(19):1972-7.
Aharon-Peretz, J., Rosenbaum, H., & Gershoni-Baruch, R. (2004). Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. The New England Journal of Medicine, 351(19), 1972-7.
Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the Glucocerebrosidase Gene and Parkinson's Disease in Ashkenazi Jews. N Engl J Med. 2004 Nov 4;351(19):1972-7. PubMed PMID: 15525722.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. AU - Aharon-Peretz,Judith, AU - Rosenbaum,Hanna, AU - Gershoni-Baruch,Ruth, PY - 2004/11/5/pubmed PY - 2004/11/13/medline PY - 2004/11/5/entrez SP - 1972 EP - 7 JF - The New England journal of medicine JO - N Engl J Med VL - 351 IS - 19 N2 - 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. SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/15525722/Mutations_in_the_glucocerebrosidase_gene_and_Parkinson's_disease_in_Ashkenazi_Jews_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa033277?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -