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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 RosaThomas 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*

*Korrespondierende/r Autor/-in für diese Arbeit

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.

OriginalspracheEnglisch
ZeitschriftMovement Disorders
Jahrgang41
Ausgabenummer4
Seiten (von - bis)1020-1027
Seitenumfang8
ISSN0885-3185
DOIs
PublikationsstatusVeröffentlicht - 04.2026

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