A molecular analysis of the GBA gene in Caucasian South Africans with Parkinson's disease

Melinda Barkhuizen*, David G. Anderson, Francois H. van der Wethuizen, Anne F. Grobler

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BackgroundThe molecular basis of Parkinson's disease in South African population groups remains elusive. To date, substitutions in the GBA gene are the most common large-effect genetic risk factor for Parkinson's disease. The primary objective of this study was to determine the prevalence of GBA substitutions in South Africans with idiopathic Parkinson's disease.

MethodsParticipants were recruited from tertiary hospitals in the Gauteng Province in South Africa. All participants were screened for substitutions in GBA exon 8-11 and the full coding region was analysed in 20 participants. Peripheral -glucocerebrosidase enzymatic activity of GBA-carriers was measured in mixed leukocytes.

ResultsOf 105 Caucasian Parkinson's disease participants (82.7% Afrikaner) with an average age of disease onset of 61.912.2years and 40 controls (age 73.4 +/- 12.4years) were included. Heterozygous GBA substitutions 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 the GBA-Parkinson's disease individuals (14.49 +/- 2.30nmol/h/mg protein vs. 15.98 +/- 3.06nmol/h/mg in control samples). GBA substitutions occur in both young-onset and late-onset Parkinson's cases in the cohort.

ConclusionMild GBA substitutions that may not cause Gaucher disease were a common risk factor for Parkinson's disease in the participant group.

Original languageEnglish
Pages (from-to)147-156
Number of pages10
JournalMolecular genetics & genomic medicine
Issue number2
Publication statusPublished - Mar 2017


  • Afrikaner
  • Gaucher disease
  • genetic screening
  • glucocerebrosidase
  • modeling
  • Parkinson's disease
  • RISK

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