Genetic and environmental factors have been proposed to influence the etiology of Parkinson’s disease (PD). A number of susceptibility genes were identified; however the exact patomechanism remains elusive. Mutations in glucocerebrosidase (GBA) gene cause Gaucher’s disease (GD) by altering glucocerebrosidase activity. GBA mutations have been reported to be the most common genetic risk factor for PD (risk increased 2-30 times depending on ethnicity). Previous studies elsewhere had major flaws by restricting analysis to the most common mutations/ignoring intronic regions. The frequency of GBA mutations in PD patients has never been examined in the Irish population. 

We prospectively recruited 314 Irish patients attending The Dublin Neurological Institute, Ireland and compared them to healthy controls. Comprehensive clinical assessment was performed. Full GBA gene sequencing analysis including inronic regions was performed in the Dept. of Neuroscience, Mayo Clinic, Jacksonville, FL.

The GBA carrier frequency was 6.7% in PD, 2.4% in controls and carrier status was associated with 3-fold increased PD risk. We identified a number of potentially pathogenic mutations including a p.G195E substitution and a p.G377C variant. The p.G377C variant was described in one case study of Gaucher’s disease from Northern Ireland as a compound heterozygote, but not in PD. Both variants will be discussed in detail. On genotype-phenotype assessment hallucinations, dyskinesia and dystonia were more prevalent in GBA-PD.