title: Glucocerebrosidase mutations are not found in association with LRRK2 G2019S in subjects with parkinsonism.
abstract: Alteration G2019S in the leucine-rich repeat kinase 2 gene (LRRK2) has been identified in several populations of patients with parkinsonism, including Ashkenazi Jewish subjects with Parkinson disease. Mutations in glucocerebrosidase (GBA), the enzyme deficient in Gaucher disease, are also identified at an increased frequency among Parkinson probands, including those of Ashkenazi Jewish ancestry. A Taqman Assay-by-Design SNP genotyping strategy was utilized to establish whether G2019S was found in association with GBA mutations. Among 37 subjects with parkinsonism who were heterozygous for a GBA mutation, none carried G2019S. Furthermore, G2019S was not found in 18 patients with Gaucher disease who developed parkinsonian manifestations and 11 other Gaucher probands with parkinsonism in a first degree relative. Among 45 patients with Gaucher disease without a history of parkinsonism, one G2019S carrier was found. These findings suggest that GBA and LRRK2 mutations are discrete risk factors for parkinsonism in both Ashkenazi Jewish and non-Jewish subjects.
authors.affiliation: Section on Molecular Neurogenetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eblan
authors.forename: Sonja
authors.initials: S
authors.lastname: Scholz
authors.forename: Barbara
authors.initials: B
authors.lastname: Stubblefield
authors.forename: Usha
authors.initials: U
authors.lastname: Gutti
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Hruska
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
mesh_terms: D019943:Amino Acid Substitution; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics; D006580:Genetic Carrier Screening; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005962:Glucosylceramidase