OBJECTIVE: To evaluate the frequency of glucocerebrosidase (GBA) mutations in cases and controls enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. METHODS: We sequenced all exons of the GBA gene in 278 Parkinson disease (PD) cases and 179 controls enrolled in GEPD, with a wide range of age at onset (AAO), and that included a subset of 178 Jewish cases and 85 Jewish controls. Cases and controls were recruited without knowledge of family history of PD, and cases were oversampled in the AAO < 50 years category. RESULTS: 13.7% of PD cases (38/278) carried GBA mutations, compared with 4.5% of controls (8/179) (odds ratio [OR] 3.4, 95% CI 1.5 to 7.4). The frequency of GBA mutations was 22.2% in 90 cases with AAO < or = 50 years, compared with 9.7% in 185 cases with AAO > 50 years (OR 2.7, 95% CI 1.3 to 5.3). Adjusting for age at the time of evaluation, sex, family history of PD, and Jewish ancestry, GBA carriers had a 1.7-year-earlier AAO of PD (95% CI 0.5 to 3.3, p < 0.04) than noncarriers. The average AAO of PD was 2.5 years earlier in carriers with an AAO < or = 50 years compared with noncarriers (95% CI 0.6 to 4.5, p < 0.01) and this was not seen in the AAO > 50 years group. The frequency of GBA mutations was higher in a subset of 178 cases that reported four Jewish grandparents (16.9%) than in cases who did not report Jewish ancestry (8.0%) (p < 0.01). Nine different GBA mutations were identified in PD cases, including 84insGG, E326K, T369M, N370S, D409H, R496H, L444P, RecNciI, and a novel mutation, P175P. CONCLUSIONS: This study suggests that the Glucocerebrosidase gene may be a susceptibility gene for Parkinson disease and that Glucocerebrosidase mutations may modify age at onset.
OBJECTIVE: To evaluate the frequency of glucocerebrosidase (GBA) mutations in cases and controls enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. METHODS: We sequenced all exons of the GBA gene in 278 Parkinson disease (PD) cases and 179 controls enrolled in GEPD, with a wide range of age at onset (AAO), and that included a subset of 178 Jewish cases and 85 Jewish controls. Cases and controls were recruited without knowledge of family history of PD, and cases were oversampled in the AAO < 50 years category. RESULTS: 13.7% of PD cases (38/278) carried GBA mutations, compared with 4.5% of controls (8/179) (odds ratio [OR] 3.4, 95% CI 1.5 to 7.4). The frequency of GBA mutations was 22.2% in 90 cases with AAO < or = 50 years, compared with 9.7% in 185 cases with AAO > 50 years (OR 2.7, 95% CI 1.3 to 5.3). Adjusting for age at the time of evaluation, sex, family history of PD, and Jewish ancestry, GBA carriers had a 1.7-year-earlier AAO of PD (95% CI 0.5 to 3.3, p < 0.04) than noncarriers. The average AAO of PD was 2.5 years earlier in carriers with an AAO < or = 50 years compared with noncarriers (95% CI 0.6 to 4.5, p < 0.01) and this was not seen in the AAO > 50 years group. The frequency of GBA mutations was higher in a subset of 178 cases that reported four Jewish grandparents (16.9%) than in cases who did not report Jewish ancestry (8.0%) (p < 0.01). Nine different GBA mutations were identified in PD cases, including 84insGG, E326K, T369M, N370S, D409H, R496H, L444P, RecNciI, and a novel mutation, P175P. CONCLUSIONS: This study suggests that the Glucocerebrosidase gene may be a susceptibility gene for Parkinson disease and that Glucocerebrosidase mutations may modify age at onset.
Authors: Rüdiger Hilker; Christine Klein; Katja Hedrich; Laurie J Ozelius; Peter Vieregge; Karl Herholz; Peter P Pramstaller; Wolf Dieter Heiss Journal: Neurosci Lett Date: 2002-04-19 Impact factor: 3.046
Authors: T Foroud; S K Uniacke; L Liu; N Pankratz; A Rudolph; C Halter; C Shults; K Marder; P M Conneally; W C Nichols Journal: Neurology Date: 2003-03-11 Impact factor: 9.910
Authors: N Tayebi; M Callahan; V Madike; B K Stubblefield; E Orvisky; D Krasnewich; J J Fillano; E Sidransky Journal: Mol Genet Metab Date: 2001-08 Impact factor: 4.797
Authors: K Hedrich; K Marder; J Harris; M Kann; T Lynch; H Meija-Santana; P P Pramstaller; E Schwinger; S B Bressman; S Fahn; C Klein Journal: Neurology Date: 2002-04-23 Impact factor: 9.910
Authors: Sofia A Oliveira; William K Scott; Eden R Martin; Martha A Nance; Ray L Watts; Jean P Hubble; William C Koller; Rajesh Pahwa; Matthew B Stern; Bradley C Hiner; William G Ondo; Fred H Allen; Burton L Scott; Christopher G Goetz; Gary W Small; Frank Mastaglia; Jeffrey M Stajich; Fengyu Zhang; Michael W Booze; Michelle P Winn; Lefkos T Middleton; Jonathan L Haines; Margaret A Pericak-Vance; Jeffery M Vance Journal: Ann Neurol Date: 2003-05 Impact factor: 10.422
Authors: Andrew West; Magali Periquet; Sarah Lincoln; Christoph B Lücking; David Nicholl; Vincenzo Bonifati; Nina Rawal; Thomas Gasser; Ebba Lohmann; Jean-François Deleuze; Demetrius Maraganore; Allan Levey; Nick Wood; Alexandra Dürr; John Hardy; Alexis Brice; Matt Farrer Journal: Am J Med Genet Date: 2002-07-08
Authors: Judit Várkonyi; Hanna Rosenbaum; Nicole Baumann; Jennifer J MacKenzie; Zsuzsa Simon; Judith Aharon-Peretz; Jamie M Walker; Nahid Tayebi; Ellen Sidransky Journal: Am J Med Genet A Date: 2003-02-01 Impact factor: 2.802