title: A molecular analysis of theGBAgene in Caucasian South Africans with Parkinson's disease.
abstract: BACKGROUND
  The molecular basis of Parkinson's disease in South African population groups remains elusive. To date, substitutions in theGBAgene are the most common large-effect genetic risk factor for Parkinson's disease. The primary objective of this study was to determine the prevalence ofGBAsubstitutions in South Africans with idiopathic Parkinson's disease.
  
  
  METHODS
  Participants were recruited from tertiary hospitals in the Gauteng Province in South Africa. All participants were screened for substitutions inGBAexon 8-11 and the full coding region was analysed in 20 participants. Peripheralβ-glucocerebrosidase enzymatic activity ofGBA-carriers was measured in mixed leukocytes.
  
  
  RESULTS
  Of 105 Caucasian Parkinson's disease participants (82.7% Afrikaner) with an average age of disease onset of 61.9 ± 12.2 years and 40 controls (age 73.4 ± 12.4 years) were included. HeterozygousGBAsubstitutions were identified in 12.38% of affected participants (p.G35A, p.E326K, p.I368T, p.T369M, p.N370S, p.P387L and p.K441N) and 5.00% of controls (p.E326K and p.T369M). The substitutions ranged from predicted benign to moderately damaging; with p.E326K and p.T369M most prevalent, followed by the Afrikaner Gaucher disease substitution p.P387L. Severe Gaucher disease mutations, like p.L444P, were absent in this cohort. Enzyme activity analysis revealed a nonsignificant reduction in theGBA-Parkinson's disease individuals (14.49 ± 2.30 nmol/h/mg protein vs. 15.98 ± 3.06 nmol/h/mg in control samples).GBAsubstitutions occur in both young-onset and late-onset Parkinson's cases in the cohort.
  
  
  CONCLUSIONS
  MildGBAsubstitutions that may not cause Gaucher disease were a common risk factor for Parkinson's disease in the participant group.
authors.affiliation: DST/NWU Preclinical Drug Development PlatformNorth-West UniversityPotchefstroom2520South Africa; Department of PaediatricsSchool for Mental Health and NeuroscienceMaastricht UniversityMaastricht6229The Netherlands.
authors.forename: Melinda
authors.identifier: 0000-0002-9952-7085
authors.initials: M
authors.lastname: Barkhuizen
authors.affiliation: Department of Neurology University of the Witwatersrand Donald Gordon Medical Centre Johannesburg 2193 South Africa.
authors.forename: David G
authors.initials: DG
authors.lastname: Anderson
authors.affiliation: Human Metabolomics North-West University Potchefstroom 2520 South Africa.
authors.forename: Francois H
authors.initials: FH
authors.lastname: van der Westhuizen
authors.affiliation: DST/NWU Preclinical Drug Development Platform North-West University Potchefstroom 2520 South Africa.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Grobler
keywords: Afrikaner; Gaucher disease; Parkinson's disease; genetic screening; glucocerebrosidase; modeling