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

Lookup NU author(s): Professor Nicola PaveseORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.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.

Publication metadata

Author(s): Ganoza CA, Westenberger A, Paul JJ, Curado F, Rennecke J, Mannepalli S, Zonic E, Saravanakumar D, Paknia O, Al-Ali R, Laabs B-H, Csoti I, Valzania F, Vandenberghe W, Reetz K, Afshari M, Hassin-Baer S, Fonoff ET, Gruber D, de Rosa A, Musacchio T, de Carvalho Aguiar P, Negrotti A, Tumas V, Gomez-Esteban JC, Gurevich T, Pavese N, Kulisevsky J, Sammler E, Klein C, Bauer P, Beetz C

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2026

Volume: 41

Issue: 4

Pages: 1020-1027

Print publication date: 01/04/2026

Online publication date: 24/12/2025

Acceptance date: 01/12/2025

Date deposited: 08/01/2026

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/mds.70161

DOI: 10.1002/mds.70161

Data Access Statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions

PubMed id: 41439479

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