Parkinson's disease phenotype is influenced by the severity of the mutations in the GBA gene

Avner Thaler*, Noa Bregman, Tanya Gurevich, Tamara Shiner, Yonatan Dror, Ofir Zmira, Ziv Gan-Or, Anat Bar-Shira, Mali Gana-Weisz, Avi Orr-Urtreger, Nir Giladi, Anat Mirelman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Objective: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations. Methods: Patients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype. Results: A total of 355 PD patients participated in this study; 152 idiopathic PD patients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005). Discussion: Motor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.

Original languageEnglish
Pages (from-to)45-49
Number of pages5
JournalParkinsonism and Related Disorders
StatePublished - Oct 2018


FundersFunder number
Chief Scientist Department of Health, Israel
Israeli Science Foundation
Israeli Science Foundation Legacy Heritage Fund
Kahn Foundation Israel
National Institutes of Health
Michael J. Fox Foundation for Parkinson's Research
ALS Association
National Park Foundation
National Parkinson Foundation
National Pancreas Foundation
Seventh Framework Programme
Israel Science Foundation
Ministry of Science and Technology, Israel


    • GBA
    • Parkinson's disease


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