title: Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada.
abstract: BACKGROUND
  Mutations in the β-glucocerebrosidase gene (GBA) have been implicated as a risk factor for Parkinson's disease (PD). However, GBA mutations in PD patients of different ethnic origins were reported to be inconsistent.
  
  
  METHODS
  We sequenced all exons of the GBA gene in 225 PD patients and 110 control individuals from Eastern Canada.
  
  
  RESULTS
  Two novel GBA variants of c.-119 A/G and S(-35)N, five known GBA mutations of R120W, N370S, L444P, RecNciI and RecTL mutation (del55/D409H/RecNciI) as well as two non-pathological variants of E326K and T369M were identified from PD patients while only one mutation of S13L and two non-pathological variants of E326K and T369M were found in the control individuals. The frequency of GBA mutations within PD patients (4.4%) is 4.8 times higher than the 0.91% observed in control individuals (X(2) = 2.91, p = 0.088; odds ratio = 4.835; 95% confidence interval = 2.524-9.123). The most common mutations of N370S and L444P accounted for 36.0% (9/25) of all the GBA mutations in this Eastern Canadian PD cohort. The frequency (6.67%) of E326K and T369M in PD patients is comparable to 7.27% in control individuals (X(2) = 0.042, p = 0.8376), further supporting that these two variants have no pathological effects on PD. Phenotype analysis showed that no significant difference in family history, age at onset and cognitive impairment was identified between the GBA mutation carriers and non-GBA mutation carriers.
  
  
  CONCLUSIONS
  GBA mutations were found to be a common genetic risk factor for PD in Eastern Canadian patients.
authors.affiliation: a 1 Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital , Taishan Medical University , Liaocheng , China.|b 2 Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital , Taishan Medical University , Liaocheng , China.
authors.forename: Fabin
authors.initials: F
authors.lastname: Han
authors.affiliation: c 3 Department of Medicine, The Ottawa Hospital , University of Ottawa , Ottawa , Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Grimes
authors.affiliation: c 3 Department of Medicine, The Ottawa Hospital , University of Ottawa , Ottawa , Canada.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: a 1 Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital , Taishan Medical University , Liaocheng , China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: a 1 Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital , Taishan Medical University , Liaocheng , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.affiliation: a 1 Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital , Taishan Medical University , Liaocheng , China.
authors.forename: Na
authors.initials: N
authors.lastname: Song
authors.affiliation: a 1 Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital , Taishan Medical University , Liaocheng , China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Wu
authors.affiliation: d 4 Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute , University of Ottawa , Ottawa , Canada.
authors.forename: Lemuel
authors.initials: L
authors.lastname: Racacho
authors.affiliation: d 4 Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute , University of Ottawa , Ottawa , Canada.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
mesh_terms: D000368:Aged; D000483:Alleles; D002170:Canada; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005962:Glucosylceramidase
keywords: Parkinson's disease (PD); frequency; glucocerebrosidase (GBA); mutation; sequencing