A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease

Nurit Omer, Nir Giladi, Tanya Gurevich, Anat Bar-Shira, Mali Gana-Weisz, Orly Goldstein, Meir Kestenbaum, Jesse M. Cedarbaum, Avi Orr-Urtreger, Anat Mirelman, Avner Thaler

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Background: The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2-PD and more severe among patients with GBA-PD; however, whether an additive phenotypical effect occurs among dual-mutation carriers requires validation. Objective: The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single-mutation presentation. Methods: Patients with PD were genotyped for the G2019S-LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA-PD, severe GBA-PD, LRRK2-PD, and LRRK2+GBA-PD. Clinical symptoms were evaluated using performance-based measures. Results: A total of 1090 patients with idiopathic PD, 155 patients with LRRK2-PD, 155 patients with mild GBA-PD, 56 patients with severe GBA-PD, and 27 patients with LRRK2+GBA-PD participated in this study. The patients with LRRK2-PD and LRRK2+GBA-PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA-PD. Conclusions: Patients with LRRK2+GBA-PD were symptomatically similar to patients with LRRK2-PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation.

Original languageEnglish
Pages (from-to)1249-1253
Number of pages5
JournalMovement Disorders
Issue number7
StatePublished - 1 Jul 2020
Externally publishedYes


  • GBA
  • LRRK2
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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