The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population

Lara M. Lange; Kristin Levine; Susan H. Fox; Connie Marras; Nazish Ahmed; Nicole Kuznetsov; Dan Vitale; Hirotaka Iwaki; Katja Lohmann; Luca Marsili; Alberto J. Espay; Peter Bauer; Christian Beetz; Jessica Martin; Stewart A. Factor; Lenora A. Higginbotham; Honglei Chen; Hampton Leonard; Mike A. Nalls; Niccolo E. Mencacci; Huw R. Morris; Andrew B. Singleton; Christine Klein; Cornelis Blauwendraat; Zih-Hua Fang; Sulev Koks; Global Parkinson’s Genetics Program (GP2)

doi:10.1038/s41531-025-00896-2

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The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population

Journal article

Open access

Peer reviewed

The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population

Lara M. Lange, Kristin Levine, Susan H. Fox, Connie Marras, Nazish Ahmed, Nicole Kuznetsov, Dan Vitale, Hirotaka Iwaki, Katja Lohmann, Luca Marsili, …

NPJ Parkinson's Disease, Vol.11(1), 58

2025

DOI: https://doi.org/10.1038/s41531-025-00896-2

PMID: 40133296

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Abstract

631/208/737

692/617/375/1718

Article

Biomedical and Life Sciences

Biomedicine

General

Neurology

Neurosciences

LRRK2-PD represents the most common form of autosomal dominant Parkinson’s disease. We identified the LRRK2 p.L1795F variant in three families and six additional unrelated cases using genetic data from over 50,000 individuals. Carriers with available genotyping data shared a common haplotype. The clinical presentation resembles other LRRK2-PD forms. Combined with published functional evidence showing strongly enhanced LRRK2 kinase activity, we provide evidence that LRRK2 p.L1795F is pathogenic.

Details

Title: The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population
Authors/Creators: Lara M. Lange - University of Lübeck
Kristin Levine - Data Tecnica International (United States)
Susan H. Fox - Toronto Western Hospital
Connie Marras - Toronto Western Hospital
Nazish Ahmed - University of Toronto
Nicole Kuznetsov - National Institute of Neurological Disorders and Stroke
Dan Vitale - Data Tecnica International (United States)
Hirotaka Iwaki - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, DataTecnica, Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health
Katja Lohmann - University of Lübeck
Luca Marsili - University of Cincinnati
Alberto J. Espay - University of Cincinnati
Peter Bauer - Centogene (Germany)
Christian Beetz - Centogene (Germany)
Jessica Martin - National Institute of Neurological Disorders and Stroke
Stewart A. Factor - Emory University
Lenora A. Higginbotham - Emory University
Honglei Chen - Michigan State University
Hampton Leonard - DataTecnica, Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health
Mike A. Nalls - DataTecnica, Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health
Niccolo E. Mencacci - Northwestern University
Huw R. Morris - University College London
Andrew B. Singleton - National Institute on Aging
Christine Klein - University of Lübeck
Cornelis Blauwendraat - National Institute of Neurological Disorders and Stroke
Zih-Hua Fang - German Center for Neurodegenerative Diseases
Sulev Koks - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
Global Parkinson’s Genetics Program (GP2)
Publication Details: NPJ Parkinson's Disease, Vol.11(1), 58
Publisher: Nature Publishing Group UK
Number of pages: 10
Grant note: Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation) (https://doi.org/10.13039/100000864) Aligning Science Across Parkinson’s Initiative Aligning Science Across Parkinson’s (ASAP) Global Parkinson’s Genetics Program (GP2) NIH CENTOGENE research support from the NIH (1K08NS131581), the Parkinson's Foundation and the Aligning Science Across Parkinson’s (ASAP) Global Parkinson's Genetics Program (GP2) Parkinson's Foundation (Parkinson's Foundation, Inc.) (https://doi.org/10.13039/100013301)
Identifiers: 991005759433407891
Murdoch Affiliation: Genomics Core Research Facility; Personalised Medicine Centre; Murdoch University; Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article
Note: Sulev Koks appears courtesy of the Global Parkinson’s Genetics Program (GP2)

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.67 Parkinson's Disease
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior