Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients
Por:
Ganoza, CA, Westenberger, A, Paul, JJ, Curado, F, Rennecke, J, Mannepalli, S, Zonic, E, Saravanakumar, D, Paknia, O, Al-Ali, R, Laabs, B, Csoti, I, Valzania, F, Vandenberghe, W, Reetz, K, Afshari, M, Hassin-Baer, S, Fonoff, ET, Gruber, D, de Rosa, A, Musacchio, T, Aguiar, PD, Negrotti, A, Tumas, V, Gomez-Esteban, JC, Gurevich, T, Pavese, N, Kulisevsky, J, Sammler, E, Klein, C, Bauer, P, Beetz, C
Publicada:
1 abr 2026
Ahead of Print:
1 dic 2025
Resumen:
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. (c) 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Filiaciones:
Ganoza, CA:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Westenberger, A:
Univ Lubeck, Inst Neurogenet, Lubeck, Germany
Paul, JJ:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Curado, F:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Rennecke, J:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Mannepalli, S:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Zonic, E:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Saravanakumar, D:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Paknia, O:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Al-Ali, R:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Arcensus GmbH, Rostock, Germany
Laabs, B:
Univ Lubeck, Univ Med Ctr Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany
Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany
Csoti, I:
Gertrudis Klin Biskirchen, Leun Biskirchen, Germany
Valzania, F:
Azienda Unita Sanit Locale IRCCS Reggio Emilia, Neuromotor & Rehabil Dept, Neurol Unit, Reggio Emilia, Italy
Vandenberghe, W:
Univ Hosp Leuven, Dept Neurol, Leuven, Belgium
Katholieke Univ Leuven, Dept Neurosci, Leuven, Belgium
Reetz, K:
Rhein Westfal TH Aachen, Dept Neurol, Sect Neurodegenerat, Aachen, Germany
Res Ctr Julich, JARA BRAIN Inst Mol Neurosci & Neuroimaging, Julich, Germany
Afshari, M:
Univ Illinois, Dept Neurol & Rehabil, Chicago, IL USA
Hassin-Baer, S:
Tel Aviv Univ, Fac Med & Hlth Sci Med, Tel Aviv, Israel
Chaim Sheba Med Ctr, Movement Disorders Inst, Ramat Gan, Israel
Fonoff, ET:
Hosp Sirio Libanes, Lab Neurosci, Sao Paulo, Brazil
Univ Sao Paulo, Dept Neurol, Med Sch, Sao Paulo, Brazil
Gruber, D:
Movement Disorders Clin, Beelitz, Germany
de Rosa, A:
Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Naples, Italy
Musacchio, T:
Wurzburg Univ Hosp, Dept Neurol, Wurzburg, Germany
Aguiar, PD:
Hosp Israelita Albert Einstein, Sao Paulo, Brazil
Negrotti, A:
Univ Hosp Parma, Dept Gen & Specialized Med, Neurol Unit, Parma, Italy
Tumas, V:
Univ Sao Paulo, Dept Neurosci & Behav Sci, Ribeirao Preto Med Sch, Sao Paulo, Brazil
Gomez-Esteban, JC:
BioBizkaia Res Inst, Neurodegenerat Dis Grp, Baracaldo, Spain
Gurevich, T:
Tel Aviv Univ, Neurol Inst, Tel Aviv Sourasky Med Ctr, Movement Disorders Unit, Tel Aviv, Israel
Pavese, N:
Newcastle Univ, Clin Ageing Res Unit, Newcastle, England
Kulisevsky, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Movement Disorders Unit, Barcelona, Spain
Sammler, E:
Univ Dundee, MRC, Prot Phosphorylat & Ubiquitylat Unit, Dundee, Scotland
Univ Dundee, Sch Med, Div Neurosci, Dundee, Scotland
Klein, C:
Univ Lubeck, Inst Neurogenet, Lubeck, Germany
Bauer, P:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Beetz, C:
CENTOGENE GmbH, Str 7, D-18055 Rostock, Germany
Chaim Sheba Med Ctr, Dept Neurol, Ramat Gan, Israel
Green Submitted, hybrid
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