Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease

• Published in: The New England journal of medicine Vol. 361; no. 17; pp. 1651 - 1661
• Main Authors: Sidransky, E, Nalls, M.A, Aasly, J.O, Aharon-Peretz, J, Annesi, G, Barbosa, E.R, Bar-Shira, A, Berg, D, Bras, J, Brice, A, Chen, C.-M, Clark, L.N, Condroyer, C, De Marco, E.V, Dürr, A, Eblan, M.J, Fahn, S, Farrer, M.J, Fung, H.-C, Gan-Or, Z, Gasser, T, Gershoni-Baruch, R, Giladi, N, Griffith, A, Gurevich, T, Januario, C, Kropp, P, Lang, A.E, Lee-Chen, G.-J, Lesage, S, Marder, K, Mata, I.F, Mirelman, A, Mitsui, J, Mizuta, I, Nicoletti, G, Oliveira, C, Ottman, R, Orr-Urtreger, A, Pereira, L.V, Quattrone, A, Rogaeva, E, Rolfs, A, Rosenbaum, H, Rozenberg, R, Samii, A, Samaddar, T, Schulte, C, Sharma, M, Singleton, A, Spitz, M, Tan, E.-K, Tayebi, N, Toda, T, Troiano, A.R, Tsuji, S, Wittstock, M, Wolfsberg, T.G, Wu, Y.-R, Zabetian, C.P, Zhao, Y, Ziegler, S.G
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 22.10.2009
• Subjects: Adult and adolescent clinical studies; Aged; Biological and medical sciences; Case-Control Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; General aspects; Genotype; Glucosylceramidase - genetics; Humans; Jews - genetics; Logistic Models; Medical sciences; Middle Aged; Minority & ethnic groups; Multivariate Analysis; Mutation; Neurology; Odds Ratio; Organic mental disorders. Neuropsychology; Parkinson Disease - genetics; Parkinson's disease; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Studies; Nervous system diseases; Enzyme; Multicenter study; Parkinson disease; Cerebral disorder; Glycosylases; Medicine; Glycosidases; Central nervous system disease; Hydrolases; Genetics; Degenerative disease; Glucosylceramidase; Mutation; Extrapyramidal syndrome
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0901281

In this international collaborative study, mutations in the gene for glucocerebrosidase ( GBA ), a deficiency of which causes Gaucher's disease, were much more likely to be detected in patients with Parkinson's disease than in controls, confirming that there is a strong association between GBA mutations and Parkinson's disease. Mutations in the gene for glucocerebrosidase ( GBA ), a deficiency of which causes Gaucher's disease, were much more likely to be detected in patients with Parkinson's disease than in controls, confirming that there is a strong association between GBA mutations and Parkinson's disease. Several lines of evidence suggest an association between parkinsonism and mutations in the gene encoding the lysosomal enzyme glucocerebrosidase ( GBA ), which is deficient in patients with Gaucher's disease. In this rare mendelian disorder, lysosomal accumulation of glucocerebroside results in a broad spectrum of disease manifestations including hepatosplenomegaly, anemia, thrombocytopenia, bone disease, and, at times, neurologic involvement. 1 , 2 Multiple independent studies have reported an increased frequency of GBA mutations in various cohorts of patients with parkinsonism. 3 – 21 However, several genomewide association studies have not identified this locus, and the degree of association has remained somewhat unclear, as many studies . . .