Session Information
Date: Wednesday, June 7, 2017
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Exhibit Hall C
Objective: To assess genotype-phenotype relationship between mild and severe GBA mutation carriers among patients with Parkinson’s disease
Background: Mutations in the Glucocerebrocidase gene (GBA) are a well-established risk factor for Parkinson disease (PD). GBA-associated PD (GBA-PD) seems to have a more severe clinical phenotype than idiopathic PD. However, differences in clinical manifestation between patients who carry severe and mild mutations in the GBA gene have yet to be reported.
Methods: We assessed motor, cognitive, olfactory and autonomic functions in a cohort of Ashkenazi Jewish PD patients who were screened for seven common mutations in the GBA gene. Differences in clinical manifestation were compared between patients with no known mutations (iPD), patients with mild GBA heterozygote PD (mGBA-PD), severe GBA heterozygote PD (sGBA-PD) and patients with PD, homozygote or compound hetrozygotes GBA carriers (GD-PD).
Results:
149 iPD, 139 mGBA-PD, 39 sGBA-PD and 25 GD-PD participated in the study. Worst motor and cognitive performance, olfaction and depression were related to GBA mutations (p<0.03). Even when adjusted to disease duration, performance deteriorated based on mutation with worst performance observed in the GD-PD group followed by the sGBA-PD and mGBA-PD. Severity of mutation was also associated with more dyskinesias (p=0.02), hallucinations (p<0.001) and higher intake of dopaminergic medications (p<0.001). When analysis was adjusted for medication intake, GD-PD and sGBA-PD patients still presented with more hallucinations (p=0.012) than mGBA-PD and iPD.
Conclusions: A “dose” like effect was observed in clinical manifestation in relation to genotype, with more severe disease manifestation in severe GBA mutation carriers and GD-PD than mild GBA-PD and iPD. These findings have important implications for patients care.
To cite this abstract in AMA style:
A. Thaler, T. Gurevich, A. Ezra, M. Kestenbaum, N. Giladi, A. Mirelman. Genotype-phenotype correlations in Parkinson disease patients who carry mutations in the GBA gene. [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/genotype-phenotype-correlations-in-parkinson-disease-patients-who-carry-mutations-in-the-gba-gene/. Accessed May 15, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/genotype-phenotype-correlations-in-parkinson-disease-patients-who-carry-mutations-in-the-gba-gene/