Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients.

BACKGROUND

Parkinsonism may be observed in multiple neurodegenerative diseases, including GRN-associated frontotemporal dementia (FTD-GRN), complicating the differential diagnosis of Parkinson's disease (PD).

OBJECTIVES

To investigate the presence of GRN variants in a large group of PD patients.

METHODS

We analyzed GRN variants in >18,500 PD patients and compared sociodemographic, genetic, and clinical data between individuals with and without GRN variants.

RESULTS

Twenty-four (0.13%) PD patients harbored 16 unique pathogenic or likely pathogenic GRN variants. Our GRN variant-positive PD patients had a higher male-to-female ratio and a younger age at onset compared with FTD-GRN patients reported in the literature. Patients with GRN variants showed higher rates of impaired olfactory function and more severe motor symptoms than GRN variant-negative patients.

CONCLUSIONS

FTD-GRN may be indistinguishable from PD. Therefore, comprehensive genetic testing, including GRN analysis, is recommended for patients with clinically diagnosed parkinsonism/PD to guide disease management and prognosis. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.