title: Mutations in the glucocerebrosidase gene are responsible for Chinese patients with Parkinson's disease.
abstract: Pathological mutations in the glucocerebrosidase gene (GBA) have been suggested to be associated with Parkinson's disease (PD) in various ethnic populations. Most studies on Chinese PD patients have only screened the N370S and L444P mutations in the GBA gene. To investigate the GBA mutations in Chinese population, we performed complete sequencing of the GBA gene in 184 Chinese PD patients and 130 Chinese control individuals. As a result, we identified three novel and nine reported GBA mutations. The novel mutations include 5-bp deletion (c.334_338delCAGAA), L264I and L314V and the nine reported GBA mutations are R163Q, F213I, E326K, S364S, F347L, V375L, L444P, RecNciI and Q497R. The novel 5-bp deletion (CAGAA) produces a short truncated GBA protein of 142 amino acids, which loses major function domains of the 536 amino acids. Our data also reveals that the frequency of GBA mutations within this Chinese PD cohort was 8.7%, which is significantly higher than 1.54% observed in the Chinese control cohort (χ(2) = 7.22, P = 0.0072; odds ratio (OR) = 6.095, 95% confidence interval of OR = 1.546-24.030). The most common L444P mutation accounts 2.74%, which confer more genetic risk for PD in this Chinese population. In conclusion, novel and known GBA mutations were identified and were found to be associated to PD in this Chinese population.
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: 1] Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China [2] Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Dianrong
authors.initials: D
authors.lastname: Gong
authors.affiliation: Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Huaiqian
authors.initials: H
authors.lastname: Qu
authors.affiliation: Department of Medicine, The Ottawa Hospital, University of Ottawa, Ontario, Canada.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Neurology, Department of Neurology, The Affiliated Reijing Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
authors.affiliation: 1] Centre for Stem cells and Regenerative Medicine, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China [2] Department of Neurology, The Affiliated Liaocheng Hospital/Liaocheng People's Hospital, Taishan Medical University, Shandong, China.
authors.forename: Fabin
authors.initials: F
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D005962:Glucosylceramidase