The LRRK2 p.L1795F variant causes Parkinson’s disease in the European population
Lange L.M. Levine K. Fox S.H. Marras C. Ahmed N. Kuznetsov N. Vitale D. Iwaki H. Lohmann K. Marsili L. Espay A.J. Bauer P. Beetz C. Martin J. Factor S.A. Higginbotham L.A. Chen H. Leonard H. Nalls M.A. Mencacci N.E. Morris H.R. Singleton A.B. Klein C. Blauwendraat C. Fang Z.-H. Atadzhanov M. Nguyen T. Nguyen D. Koretsky M. Makarious M.B. Faghri F. Beach T. Xie T. Dumanis S. Walker R. Alcalay R. Albin R. Lubbe S. Puckelwartz M.J. Farrer M. Dean M. Shulman L. Ruffrage L. Chahine L.M. Marek K. Markopoulou K. Kieburtz K. Nuytemans K. Galvelis K.G. Shulman J. Jankovic J. Williamson J. Inca-Martinez M. Mata I.F. Serrano G.E. Riley E. Shiamim E. Song Y. Kim J.J. Hernandez D. Hall D. Foroud T. Wegel C. Ibanez L. Cruchaga C. Jonas C. Sobering A.K. Sherer T. Chowdhury S. Louie N. Kuhl M. Murphy K. Solle J.C. Comart C. Fiske B. Casey B. Siddiqi B. O’Grady A. Sarmiento I.J.K. Bandres-Ciga S. Screven L. Andersh K. Pantazis C.B. Stott S. Love S. Lewis P.A. Williams N. Grosset D. Bale C. Carroll C. Obese V. Jasaityte S. Weil R. Kaiyrzhanov R. Okunoye O. Wood N. Rizig M. Mok K.Y. Hardy J. Houlden H. Stafford E.J. Schapira A. Schrag A. Martínez-Carrasco A. Dey S. Noyce A. Genc G. Ertan S. Çakmak Ö.Ö. Başak A.N. Ben Sassi S. Amouri R. Wu Y. Wu R.-M. Wu H.-C. Kung P.-J. Lin C.-H. Tinkhauser G. Krack P. Zweier C. Brolin K. El-Sadig S. Pastor P. Periñan M.T. Beyer K. Hoenicka J. Alvarez I. Cubo E. Kim Y.J. Jeon B. Bardien S. Carr J. Amod F. Foo J.N. Tan E.-K. Umair M. Mubarak B.A. Iakovenko E. Vinuela A. Rosales R. Doquenia M.L. Cornejo-Olivas M. Ur-Rehman S. Tan M. Pihlstrøm L. Aasly J.O. Ojo O. Okubadejo N. Sanyaolu A. Pitcher T.L. Anderson T.J. Ojha R. Tserensodnom B. Reyes-Pérez P. Rodriguez-Violante M. Martinez-Ramirez D. Mohamed W. Azmin S. Murad N.A.A. Norlinah M.I. Tay Y.W. Lim S.-Y. Ahmad-Annuar A. Tan A.H. Krüger R. Shambetova C. Kaishibayeva G. Karimova A. Shiraishi T. Hattori N. Funayama M. Schirinzi T. Parnetti L. Annesi G. Avenali M. Valente E.M. Gagliardi M. Quattrone A. Salari M. Borgohain R. Rajan R. Kukkle P.L. Pal P. KP D. Kishore A. Zhou X. Chan P. Ip N. Cheung N.Y.-F. Chan G.H.-F. Medina A. Stamelou M. Stefanis L. Tarnanas I. Dagklis I. Dadiotis E. Hadjigorgiou G. Xiromerisiou G. Akpalu A. Groppa S. Gasser T. Sharma M. Höglinger G. Hopfner F. Mollenhauer B. Illarionova A. Junker J. Trinh J. Madoev H. Vollstedt E.-J. Westenberger A. Corvol J.-C. Brice A. Zewde Y.Z. Kamel W.A. Salama M. Hernandez A. del Rio M.J. Orozco J. Arboleda G. Luo W. Chan P. Guo J. Shang H. Tang B. Chana P. Bustamante M.L. Miranda M. Olguin P. Galleguillos B.P. Fon T. Monchi O. Fon E.A. Camargos S. Tumas V. Awad P.S. Rieder C. Schumacher-Schuh A.F. Zimprich A. Koks S. Rentería M.E. Ellis M. Kumar K. Hunter J. Shepherd C.E. Tavadyan Z. Khachatryan S. Kauffman M. Gatto E.M.
December 2025Nature Research
npj Parkinsons Disease
2025#11Issue 1
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.
Text of the article Перейти на текст статьи
Institute of Neurogenetics, University of Luebeck, Luebeck, Germany
Department of Neurology, University Hospital Schleswig-Holstein, Luebeck, Germany
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
DataTecnica, Washington, DC, United States
Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
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, Toronto, ON, Canada
University of Cincinnati, Cincinnati, OH, United States
CENTOGENE GmbH, Rostock, Germany
Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States
Department of Epidemiology and Biostatistics, Michigan State University, Michigan, MI, United States
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom
UCL Movement Disorders Centre, University College London, London, United Kingdom
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Sanatorio de la Trinidad Mitre – INEBA, Buenos Aires, Argentina
Hospital JM Ramos Mejia, Buenos Aires, Argentina
Somnus Neurology Clinic, Yerevan, Armenia
Neuroscience Research Australia, Sydney, NSW, Australia
ANZAC Research Institute, Concord, NSW, Australia
Garvan Institute of Medical Research and Concord Repatriation General Hospital, Darlinghurst, NSW, Australia
Concord Hospital, Concord, NSW, Australia
QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Murdoch University, Perth, WA, Australia
Medical University Vienna, Vienna, Austria
Universidade Federal do Rio Grande do Sul / Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
University of São Paulo, São Paulo, Brazil
Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Montreal Neurological Institute, Montreal, QC, Canada
Institut universitaire de gériatrie de Montréal, Montreal, QC, Canada
McGill University, Montreal, QC, Canada
Universidad de Chile, Santiago, Chile
Fundación Diagnosis, Santiago, Chile
Faculty of Medicine Universidad de Chile, Santiago, Chile
CETRAM, Santiago, Chile
Central South University, Changsha, China
West China Hospital Sichuan University, Chengdu, China
Xiangya Hospital, Changsha, China
Capital Medical University, Beijing, China
Zhejiang University, Hangzhou, China
Universidad Nacional de Colombia, Bogotá, Colombia
Fundación Valle del Lili, Santiago De Cali, Colombia
University of Antioquia, Medellin, Colombia
University of Costa Rica, San Jose, Costa Rica
The American University in Cairo, Cairo, Egypt
Beni-Suef University, Beni Suef, Egypt
Addis Ababa University, Addis Ababa, Ethiopia
Paris Brain Institute, Paris, France
Sorbonne Université, Paris, France
University Medical Center Göttingen, Göttingen, Germany
Department of Neurology, University Hospital, LMU Munich, Munich, Germany
University of Tübingen, Tübingen, Germany
University of Mainz, Mainz, Germany
University of Ghana Medical School, Accra, Ghana
University of Thessaly, Volos, Greece
Aristotle University of Thessaloniki, Thessaloniki, Greece
Ionian University, Corfu, Greece
Biomedical research Foundation of the Academy of Athens, Athens, Greece
Diagnostic and Therapeutic Centre HYGEIA Hospital, Marousi, Greece
Hospital San Felipe, Tegucigalpa, Honduras
Queen Elizabeth Hospital, Kowloon, Hong Kong
The Hong Kong University of Science and Technology, Kowloon, Hong Kong
Aster Medcity, Kochi, India
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India
National Institute of Mental Health & Neurosciences, Bengaluru, India
Manipal Hospital, Delhi, India
All India Institute of Medical Sciences, Delhi, India
Nizam’s Institute Of Medical Sciences, Hyderabad, India
Shahid Beheshti University of Medical Science, Tehran, Iran
Magna Graecia University of Catanzaro, Catanzaro, Italy
University of Pavia, Pavia, Italy
National Research Council, Cosenza, Italy
University of Perugia, Perugia, Italy
University of Rome Tor Vergata, Rome, Italy
Juntendo University, Tokyo, Japan
Jikei University School of Medicine, Tokyo, Japan
Institute of Neurology and Neurorehabilitation, Almaty, Kazakhstan
Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan
University of Luxembourg, Luxembourg, Luxembourg
University of Malaya, Kuala Lumpur, Malaysia
Universiti Kebangsaan Malaysia, Selangor, Malaysia
UKM Medical Molecular Biology Institute, Kuala Lumpur, Malaysia
Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
International Islamic University, Kuala Lumpur, Malaysia
Tecnologico de Monterrey, Monterrey, Mexico
Instituto Nacional de Neurologia y Neurocirugia, Mexico City, Mexico
Universidad Nacional Autónoma de México, Mexico City, Mexico
Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
Tribhuvan University, Kirtipur, Nepal
University of Otago, Dunedin, New Zealand
University of Lagos, Lagos, Nigeria
Norwegian University of Science and Technology, Trondheim, Norway
Oslo University Hospital, Oslo, Norway
University of Science and Technology Bannu, Bannu, Pakistan
Universidad Cientifica del Sur, Lima, Peru
Metropolitan Medical Center, Manila, Philippines
University of Puerto Rico, San Juan, Puerto Rico
Research Center of Neurology, Moscow, Russian Federation
King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
National Neuroscience Institute, Singapore, Singapore
Nanyang Technological University, Singapore, Singapore
University of KwaZulu-Natal, Durban, South Africa
Stellenbosch University, Stellenbosch, South Africa
Seoul National University Hospital, Seoul, South Korea
Yongin Severance Hospital, Seoul, South Korea
Hospital Universitario Burgos, Burgos, Spain
University Hospital Mutua Terrassa, Barcelona, Spain
Institut de Recerca Sant Joan de Deu, Barcelona, Spain
Research Institute Germans Trias i Pujol, Barcelona, Spain
Instituto de Biomedicina de Sevilla, Seville, Spain
University Hospital Germans Trias i Pujol, Barcelona, Spain
Faculty of medicine university of Khartoum, Khartoum, Sudan
Lund University, Lund, Sweden
Inselspital Bern, University of Bern, Bern, Switzerland
University Hospital Bern, Bern, Switzerland
National Taiwan University Hospital, Taipei City, Taiwan
National Taiwan University, Taipei City, Taiwan
Chang Gung Memorial Hospital, Taoyuan City, Taiwan
National Institute Mongi Ben Hamida of Neurology, Tunis, Tunisia
Koç University, Istanbul, Turkey
Şişli Etfal Training and Research Hospital, Istanbul, Turkey
Queen Mary University of London, London, United Kingdom
University College London, London, United Kingdom
University of Plymouth, Plymouth, United Kingdom
Parkinson’s UK, London, United Kingdom
University of Glasgow, Glasgow, United Kingdom
Cardiff University, Cardiff, United Kingdom
Royal Veterinary College University of London, London, United Kingdom
University of Bristol, Bristol, United Kingdom
Cure Parkinson’s, London, United Kingdom
National Institutes of Health, Bethesda, MD, United States
The Michael J. Fox Foundation for Parkinson’s Research, New York, NY, United States
Augusta University / University of Georgia Medical Partnership, Augusta, GA, United States
Mid-Atlantic Permanente Medical Group, Bethesda, MD, United States
Washington University, St. Louis, MO, United States
Indiana University, Bloomington, IN, United States
Indiana University School of Medicine, Indianapolis, IN, United States
Rush University, Chicago, IL, United States
Kaiser Permanente, Oakland, CA, United States
Coalition for Aligning Science, Washington, WA, United States
Banner Sun Health Research Institute, Sun City, AZ, United States
Cleveland Clinic, Cleveland, OH, United States
Baylor College of Medicine, Houston, TX, United States
Parkinson’s Foundation, Princeton, NJ, United States
University of Miami Miller School of Medicine, Miami, FL, United States
Beth Israel Deaconess Medical Center, Boston, MA, United States
North Shore University Health System, Chicago, IL, United States
Institute for Neurodegenerative Disorders, New Haven, CT, United States
University of Pittsburgh, Pittsburgh, PA, United States
University of Alabama at Birmingham, Birmingham, AL, United States
University of Maryland, Baltimore, MD, United States
University of Florida – Neurology, Gainesville, FL, United States
Northwestern University, Chicago, IL, United States
University of Michigan, Ann Arbor, MI, United States
Columbia University, New York, NY, United States
James J. Peters Veterans Affairs Medical Center, New York, NY, United States
Aligning Science Across Parkinson’s, Washington, WA, United States
University of Chicago, Chicago, IL, United States
Sun Health Research Institution, Sun City, AZ, United States
Hue University, Huế, Viet Nam
University of Zambia, Lusaka, Zambia
Institute of Neurogenetics
Department of Neurology
Laboratory of Neurogenetics
DataTecnica
Center for Alzheimer’s and Related Dementias (CARD)
Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic
University of Cincinnati
CENTOGENE GmbH
Department of Neurology
Department of Epidemiology and Biostatistics
Department of Neurology
Department of Clinical and Movement Neurosciences
UCL Movement Disorders Centre
German Center for Neurodegenerative Diseases (DZNE)
Sanatorio de la Trinidad Mitre – INEBA
Hospital JM Ramos Mejia
Somnus Neurology Clinic
Neuroscience Research Australia
ANZAC Research Institute
Garvan Institute of Medical Research and Concord Repatriation General Hospital
Concord Hospital
QIMR Berghofer Medical Research Institute
Murdoch University
Medical University Vienna
Universidade Federal do Rio Grande do Sul / Hospital de Clínicas de Porto Alegre
Federal University of Health Sciences of Porto Alegre
Universidade Federal do Rio Grande do Sul
University of São Paulo
Universidade Federal de Minas Gerais
Montreal Neurological Institute
Institut universitaire de gériatrie de Montréal
McGill University
Universidad de Chile
Fundación Diagnosis
Faculty of Medicine Universidad de Chile
CETRAM
Central South University
West China Hospital Sichuan University
Xiangya Hospital
Capital Medical University
Zhejiang University
Universidad Nacional de Colombia
Fundación Valle del Lili
University of Antioquia
University of Costa Rica
The American University in Cairo
Beni-Suef University
Addis Ababa University
Paris Brain Institute
Sorbonne Université
University Medical Center Göttingen
Department of Neurology
University of Tübingen
University of Mainz
University of Ghana Medical School
University of Thessaly
Aristotle University of Thessaloniki
Ionian University
Biomedical research Foundation of the Academy of Athens
Diagnostic and Therapeutic Centre HYGEIA Hospital
Hospital San Felipe
Queen Elizabeth Hospital
The Hong Kong University of Science and Technology
Aster Medcity
Sree Chitra Tirunal Institute for Medical Sciences and Technology
National Institute of Mental Health & Neurosciences
Manipal Hospital
All India Institute of Medical Sciences
Nizam’s Institute Of Medical Sciences
Shahid Beheshti University of Medical Science
Magna Graecia University of Catanzaro
University of Pavia
National Research Council
University of Perugia
University of Rome Tor Vergata
Juntendo University
Jikei University School of Medicine
Institute of Neurology and Neurorehabilitation
Kyrgyz State Medical Academy
University of Luxembourg
University of Malaya
Universiti Kebangsaan Malaysia
UKM Medical Molecular Biology Institute
Universiti Kebangsaan Malaysia Medical Centre
International Islamic University
Tecnologico de Monterrey
Instituto Nacional de Neurologia y Neurocirugia
Universidad Nacional Autónoma de México
Mongolian National University of Medical Sciences
Tribhuvan University
University of Otago
University of Lagos
Norwegian University of Science and Technology
Oslo University Hospital
University of Science and Technology Bannu
Universidad Cientifica del Sur
Metropolitan Medical Center
University of Puerto Rico
Research Center of Neurology
King Faisal Specialist Hospital and Research Center
King Abdullah International Medical Research Center
National Neuroscience Institute
Nanyang Technological University
University of KwaZulu-Natal
Stellenbosch University
Seoul National University Hospital
Yongin Severance Hospital
Hospital Universitario Burgos
University Hospital Mutua Terrassa
Institut de Recerca Sant Joan de Deu
Research Institute Germans Trias i Pujol
Instituto de Biomedicina de Sevilla
University Hospital Germans Trias i Pujol
Faculty of medicine university of Khartoum
Lund University
Inselspital Bern
University Hospital Bern
National Taiwan University Hospital
National Taiwan University
Chang Gung Memorial Hospital
National Institute Mongi Ben Hamida of Neurology
Koç University
Şişli Etfal Training and Research Hospital
Queen Mary University of London
University College London
University of Plymouth
Parkinson’s UK
University of Glasgow
Cardiff University
Royal Veterinary College University of London
University of Bristol
Cure Parkinson’s
National Institutes of Health
The Michael J. Fox Foundation for Parkinson’s Research
Augusta University / University of Georgia Medical Partnership
Mid-Atlantic Permanente Medical Group
Washington University
Indiana University
Indiana University School of Medicine
Rush University
Kaiser Permanente
Coalition for Aligning Science
Banner Sun Health Research Institute
Cleveland Clinic
Baylor College of Medicine
Parkinson’s Foundation
University of Miami Miller School of Medicine
Beth Israel Deaconess Medical Center
North Shore University Health System
Institute for Neurodegenerative Disorders
University of Pittsburgh
University of Alabama at Birmingham
University of Maryland
University of Florida – Neurology
Northwestern University
University of Michigan
Columbia University
James J. Peters Veterans Affairs Medical Center
Aligning Science Across Parkinson’s
University of Chicago
Sun Health Research Institution
Hue University
University of Zambia
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026