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

Christian A. Ganoza; Ana Westenberger; Jefri J. Paul; Filipa Curado; Jörg Rennecke; Sumanth Mannepalli; Emir Zonic; Deepa Saravanakumar; Omid Paknia; Ruslan Al-Ali; Björn Hergen Laabs; Ilona Csoti; Franco Valzania; Wim Vandenberghe; Katrin Reetz; Mitra Afshari; Sharon Hassin-Baer; Erich Talamoni Fonoff; Doreen Gruber; Anna de Rosa; Thomas Musacchio; Patricia de Carvalho Aguiar; Anna Negrotti; Vitor Tumas; Juan Carlos Gomez-Esteban; Tanya Gurevich; Nicola Pavese; Jaime Kulisevsky; Esther Sammler; Christine Klein; Peter Bauer; Christian Beetz

doi:10.1002/mds.70161

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

Christian A. Ganoza
, Ana Westenberger
, Jefri J. Paul
, Filipa Curado
, Jörg Rennecke
, Sumanth Mannepalli
, Emir Zonic
, Deepa Saravanakumar
, Omid Paknia
, Ruslan Al-Ali
, Björn Hergen Laabs
, Ilona Csoti
, Franco Valzania
, Wim Vandenberghe
, Katrin Reetz
, Mitra Afshari
, Sharon Hassin-Baer
, Erich Talamoni Fonoff
, Doreen Gruber
, Anna de Rosa

Thomas Musacchio, Patricia de Carvalho Aguiar, Anna Negrotti, Vitor Tumas, Juan Carlos Gomez-Esteban, Tanya Gurevich, Nicola Pavese, Jaime Kulisevsky, Esther Sammler, Christine Klein, Peter Bauer, Christian Beetz (Lead / Corresponding author)

Neuroscience

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	1020-1027
Number of pages	8
Journal	Movement Disorders
Volume	41
Issue number	4
Early online date	24 Dec 2025
DOIs	https://doi.org/10.1002/mds.70161
Publication status	Published - 10 Apr 2026

Keywords

age at onset
frontotemporal dementia
FTD
genetic variants
GRN
GRN-associated frontotemporal dementia
male-to-female ratio
Parkinson's disease
parkinsonism

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.70161Licence: CC BY-NC-ND

Final published verison
© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.https://doi.org/10.1002/mds.70161
Final published version, 399 KBLicence: CC BY-NC-ND

Cite this

Ganoza, C. A., Westenberger, A., Paul, J. J., 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, E. T., Gruber, D., ... Beetz, C. (2026). Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients. Movement Disorders, 41(4), 1020-1027. https://doi.org/10.1002/mds.70161

@article{75de738805234c74a4aafab5918b3d7d,

title = "Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1\% of Parkinson's Disease Patients",

abstract = "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.",

keywords = "age at onset, frontotemporal dementia, FTD, genetic variants, GRN, GRN-associated frontotemporal dementia, male-to-female ratio, Parkinson's disease, parkinsonism",

author = "Ganoza, \{Christian A.\} and Ana Westenberger and Paul, \{Jefri J.\} and Filipa Curado and J{\"o}rg Rennecke and Sumanth Mannepalli and Emir Zonic and Deepa Saravanakumar and Omid Paknia and Ruslan Al-Ali and Laabs, \{Bj{\"o}rn Hergen\} and Ilona Csoti and Franco Valzania and Wim Vandenberghe and Katrin Reetz and Mitra Afshari and Sharon Hassin-Baer and Fonoff, \{Erich Talamoni\} and Doreen Gruber and \{de Rosa\}, Anna and Thomas Musacchio and \{de Carvalho Aguiar\}, Patricia and Anna Negrotti and Vitor Tumas and Gomez-Esteban, \{Juan Carlos\} and Tanya Gurevich and Nicola Pavese and Jaime Kulisevsky and Esther Sammler and Christine Klein and Peter Bauer and Christian Beetz",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2026",

month = apr,

day = "10",

doi = "10.1002/mds.70161",

language = "English",

volume = "41",

pages = "1020--1027",

journal = "Movement Disorders",

issn = "0885-3185",

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Ganoza, CA, Westenberger, A, Paul, JJ, Curado, F, Rennecke, J, Mannepalli, S, Zonic, E, Saravanakumar, D, Paknia, O, Al-Ali, R, Laabs, BH, 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 2026, 'Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients', Movement Disorders, vol. 41, no. 4, pp. 1020-1027. https://doi.org/10.1002/mds.70161

TY - JOUR

T1 - Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients

AU - Ganoza, Christian A.

AU - Westenberger, Ana

AU - Paul, Jefri J.

AU - Curado, Filipa

AU - Rennecke, Jörg

AU - Mannepalli, Sumanth

AU - Zonic, Emir

AU - Saravanakumar, Deepa

AU - Paknia, Omid

AU - Al-Ali, Ruslan

AU - Laabs, Björn Hergen

AU - Csoti, Ilona

AU - Valzania, Franco

AU - Vandenberghe, Wim

AU - Reetz, Katrin

AU - Afshari, Mitra

AU - Hassin-Baer, Sharon

AU - Fonoff, Erich Talamoni

AU - Gruber, Doreen

AU - de Rosa, Anna

AU - Musacchio, Thomas

AU - de Carvalho Aguiar, Patricia

AU - Negrotti, Anna

AU - Tumas, Vitor

AU - Gomez-Esteban, Juan Carlos

AU - Gurevich, Tanya

AU - Pavese, Nicola

AU - Kulisevsky, Jaime

AU - Sammler, Esther

AU - Klein, Christine

AU - Bauer, Peter

AU - Beetz, Christian

PY - 2026/4/10

Y1 - 2026/4/10

N2 - 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.

AB - 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.

KW - age at onset

KW - frontotemporal dementia

KW - FTD

KW - genetic variants

KW - GRN

KW - GRN-associated frontotemporal dementia

KW - male-to-female ratio

KW - Parkinson's disease

KW - parkinsonism

UR - https://www.scopus.com/pages/publications/105025744020

U2 - 10.1002/mds.70161

DO - 10.1002/mds.70161

M3 - Article

C2 - 41439479

AN - SCOPUS:105025744020

SN - 0885-3185

VL - 41

SP - 1020

EP - 1027

JO - Movement Disorders

JF - Movement Disorders

IS - 4

ER -

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

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Keywords

ASJC Scopus subject areas

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