Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients
Year: 2025
Type: article
Study design: Observational Study
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. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Source: Movement Disorders
DOI: 10.1002/mds.70161
Authors: 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
Institutions: Centogene (Germany), University of Lübeck, Universitätsmedizin Göttingen, University of Göttingen, Azienda Sanitaria Unità Locale di Reggio Emilia, Universitair Ziekenhuis Leuven, KU Leuven, Jülich Aachen Research Alliance, RWTH Aachen University, University of Illinois Chicago, Tel Aviv University, Sheba Medical Center, Universidade de São Paulo, Hospital Sírio-Libanês, Federico II University Hospital, University of Naples Federico II, University of Würzburg, Universitätsklinikum Würzburg, Hospital Israelita Albert Einstein, University of Parma, Ospedale di Parma, Tel Aviv Sourasky Medical Center, Newcastle University, Hospital de Sant Pau, University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit, Medical Research Council
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
OpenAlex ID: W7117129118