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

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.

Principal Investigator(s):

Author(s):
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

PubMed:
41439479
Citation:
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
Movement Disorders
2025
Dec
doi:
10.1002/mds.70161
PMID: 41439479