title: Glucocerebrosidase mutations in Thai patients with Parkinson's disease.
abstract: BACKGROUND
  GBA mutations are an important risk factor in developing Parkinson's disease (PD) worldwide. The study aimed to determine the frequency and clinical characteristics of GBA mutations in a Thai PD cohort of 480 patients and 395 control subjects.
  
  
  METHODS
  Direct sequencing of GBA was performed in all early-onset PD patients (EOPD: n = 108) and 100 PD patients with age at onset over 50 years (AAO > 50y-PD). The study subsequently screened all identified mutations in the remaining AAO > 50y-PD patients and all control subjects. Predictive factors associated with risk of developing PD were analyzed. Comparisons of clinical characteristics of PD patients with and without GBA mutations were also carried out.
  
  
  RESULTS
  Heterozygous GBA mutations were identified in 24 patients (5%) and 2 controls (0.5%). Seven identified GBA point mutations comprised p.L444P, p.N386K, p.P428S, IVS2+1G > A, IVS9+3G > C, IVS10-9_10GT > AG and c.1309delG, of which five mutations were novel. Multiple logistic regression analysis revealed that GBA mutations were more frequent in EOPD than AAO > 50y-PD groups (OR = 4.64, P < 0.022). Patients with GBA mutations had mean age at onset (43.1 ± 10.2, mean ± standard deviation) earlier than patients without GBA mutations (54.4 ± 13.9, P = 0.002). The patients with GBA mutations also had a more rapid progressive course, in which they were more likely to have higher Hoehn and Yahr staging (OR = 4.20, P = 0.006) and slightly lower means of Schwab-England ADL score [74.1 ± 17.1 vs. 81.0 ± 18.08 (OR = 0.98, 95%CI = 0.96-1.01, P = 0.162)].
  
  
  CONCLUSIONS
  GBA mutations are an important risk of PD in the Thai population. Patients having the mutations are likely to have early onset and may exhibit more rapid motor progression.
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Electronic address: teeratorn.pul@mahidol.ac.th.
authors.forename: Teeratorn
authors.initials: T
authors.lastname: Pulkes
authors.affiliation: Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Lulin
authors.initials: L
authors.lastname: Choubtum
authors.affiliation: Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sermsiri
authors.initials: S
authors.lastname: Chitphuk
authors.affiliation: Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.affiliation: Division of Neurology, Department of Medicine, Bhumibol Adulyadej Hospital, Bangkok, Thailand.
authors.forename: Sunsanee
authors.initials: S
authors.lastname: Pongpakdee
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Kongkiat
authors.initials: K
authors.lastname: Kulkantrakorn
authors.affiliation: Department of Neurology, Prasat Neurological Institute, Bangkok, Thailand.
authors.forename: Suchat
authors.initials: S
authors.lastname: Hanchaiphiboolkul
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Somsak
authors.initials: S
authors.lastname: Tiamkao
authors.affiliation: Division of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Pairoj
authors.initials: P
authors.lastname: Boonkongchuen
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005962:Glucosylceramidase
keywords: Beta-glucosidase; Early-onset Parkinson's disease; Familial Parkinson's disease; Glucocerebrosidase