npj Parkinson's Disease (Mar 2025)
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,
- the Global Parkinson’s Genetics Program (GP2)
Affiliations
- Lara M. Lange
- Institute of Neurogenetics, University of Luebeck
- Kristin Levine
- DataTecnica
- Susan H. Fox
- Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, University of Toronto
- Connie Marras
- Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, University of Toronto
- Nazish Ahmed
- Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, University of Toronto
- Nicole Kuznetsov
- DataTecnica
- Dan Vitale
- DataTecnica
- Hirotaka Iwaki
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health
- Katja Lohmann
- Institute of Neurogenetics, University of Luebeck
- Luca Marsili
- University of Cincinnati
- Alberto J. Espay
- University of Cincinnati
- Peter Bauer
- CENTOGENE GmbH
- Christian Beetz
- CENTOGENE GmbH
- Jessica Martin
- Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health
- Stewart A. Factor
- Department of Neurology, Emory University School of Medicine
- Lenora A. Higginbotham
- Department of Neurology, Emory University School of Medicine
- Honglei Chen
- Department of Epidemiology and Biostatistics, Michigan State University
- Hampton Leonard
- DataTecnica
- Mike A. Nalls
- DataTecnica
- Niccolo E. Mencacci
- Department of Neurology, Northwestern University Feinberg School of Medicine
- Huw R. Morris
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology
- Andrew B. Singleton
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health
- Christine Klein
- Institute of Neurogenetics, University of Luebeck
- Cornelis Blauwendraat
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health
- Zih-Hua Fang
- German Center for Neurodegenerative Diseases (DZNE)
- the Global Parkinson’s Genetics Program (GP2)
- DOI
- https://doi.org/10.1038/s41531-025-00896-2
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 10
Abstract
Abstract 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.
