Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort


Por: Correia Guedes L., Jesús Maestre S., Aasly A., Aasly J.O., Abramycheva N.Y., Ahmad-Annuar A., Albanese A., Alcalay R.N., Aldakheel A., Alkhairallah T., Al-Mubarak B., Al-tassan N., Alvarez V., Amami P., Annesi G., Appel-Cresswell S., Leite M.A.A., Arkadir D., Avenali M., Ferraz H.B., Bardien S., Barkhuizen M., Barrett M.J., Basak A.N., Berg D., Bilgic B., Bloem B.R., Bonifati V., Boon A.J.W., Borges V., Borngräber F., Borsche M., Bozi M., Bressman S., Brice A., Brighina L., Brockmann K., Brüggemann N., Camacho M., Belin A.C., Carr J., Cesarini M.E., Cornejo-Olivas M., Chase B., Chung S.J., Guedes L.C., Clarimon J., Clark L., Corvol J.-C., Crosiers D., Das P., de Carvalho Aguiar P., Damásio J., de Michele G., De Rosa A., Dieguez E., Dorszewska J., Ertan S., Fahn S., Farrer M.J., Fedotova E.Y., Ferese R., Ferreira J.J., Foroud T., Funayama M., Fung V.S.C., Gagliardi M., Gambardella S., Garraux G., Garrido A., Gatto E.M., Genç G., Giladi N., Gómez-Garre P., Hanagasi H., Hattori N., Hentati F., Hertz J.M., Illarioshkin S.N., Jankovic J., Januario C., Maestre S.J., Kaasinen V., Kasten M., Kataoka H., Kievit A.A., Kim Y.J., Klein C., Klivényi P., Kostic V.S., Koziorowski D., Krüger R., Kühn A.A., Kuhlenbäumer G., Kuo M.-C., Lang A.E., Lee-Chen G.-J., Lesage S., Lim J.L., Lim S.-Y., Lin C.-H., Lohmann K., Lynch T., Marder K., Markopoulou K., Martikainen M., May P., McCarthy A., Mellick G.D., Menéndez-González M., Merello M., Mir P., Mirelman A., Mollenhauer B., Briceno H.M., Morgadinho A., Morris H., Mosejova A., Nishioka K., Çakmak Ö.Ö., Olszewska D.A., Orr-Urtreger A., Pachchek S., Padmanabhan S., Periñán M.T., Petrucci S., Pimentel M.M.G., Procopio R., Pulkes T., Puschmann A., Ran C., Riess O., Ross O.A., Rossi M., Ruiz-Martinez J., Sammler E.M., Pereira J.S., Satake W., Saunders-Pullman R., Schaake S., Petersen M.S., Skorvanek M., Stefanis L., Soto-Beasley A.I., Sousa M., Spitz M., Suchowersky O., Sue C.M., Tan A.H., Tan E.-K., Thaler A., Tepgeç F., Termsarasab P., Tesson C., Toda T., Toft M., Tolosa E., Torres-Ramirez L., Tumas V., Uyguner O., Valente E.M., van de Warrenburg B., Vidailhet M., Vollstedt E.-J., Walton R.L., Waters C., Williams-Gray C.H., Winkelmann J., Wu Y.-R., Wurster I., Wszolek Z.K., Wu R.-M., Zhang B.-R., Zimprich A.

Publicada: 1 ene 2023 Ahead of Print: 1 ene 2023
Resumen:
Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Filiaciones:
Correia Guedes L.:
 Department of Neuroscience and Mental Health, Neurology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal

Jesús Maestre S.:
 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Aasly A.:
 Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway

Aasly J.O.:
 Department of Neurology, St. Olavs Hospital, Trondheim, Norway

 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway

Abramycheva N.Y.:
 Department of Neurogenetics, Research Center of Neurology, Moscow, Russian Federation

Ahmad-Annuar A.:
 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Alcalay R.N.:
 Department of Neurology, Columbia University, New York, NY, United States

Al-Mubarak B.:
 Behavioural Genetics Unit, Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Alvarez V.:
 Laboratório de Genética, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

 Instituto de Investigación

 Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

Annesi G.:
 Institute of Biomedical Research and Innovation, National Research Council, Cosenza, Italy

Appel-Cresswell S.:
 Pacific Parkinson's Research Centre, Division of Neurology, Department of Medicine, Vancouver, BC, Canada

Arkadir D.:
 Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel

Avenali M.:
 Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy

Barkhuizen M.:
 DST/NWU Preclinical Drug Development Platform, North-West University, North-West, Potchefstroom, South Africa

Berg D.:
 Department of Neurology, Christian-Albrechts-Universität, Kiel, Germany

Boon A.J.W.:
 Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands

Borges V.:
 Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil

Borngräber F.:
 Movement Disorder and Neuromodulation Unit, Charité, Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany

Borsche M.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

 Department of Neurology and Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Bozi M.:
 Parkinson's and Movement Disorders Unit, 2nd Department of Neurology of the University of Athens, Attikon Hospital, Haidari, Athens, Greece

Bressman S.:
 Department of Neurology, Beth Israel Medical Center, New York, New York, USA

Brice A.:
 Department of Neurology, Sorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France

Brighina L.:
 Department of Neurology, Milan Center for Neuroscience, University of Milano-Bicocca/San Gerardo Hospital, Monza, Italy

Brockmann K.:
 Department of Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Baden Wuerttemberg, Germany, Hertie Institute for Clinical Brain Research and German Centre for Neurodegenerative Diseases, Tuebingen, Germany

Brüggemann N.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

 Department of Neurology and Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Camacho M.:
 Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom

Belin A.C.:
 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Carr J.:
 Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

Cornejo-Olivas M.:
 Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru

Chase B.:
 Department of Neurology, NorthShore University HealthSystem, Evanston, IL, United States

Chung S.J.:
 Medical Genetic Center, Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Clarimon J.:
 Department of Neurology, Biomedical Research Institute IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Clark L.:
 Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, New York, USA

Corvol J.-C.:
 Sorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Neurology, Paris, France

Crosiers D.:
 Department of Neurology, Antwerp University Hospital, Edegem, Belgium

Das P.:
 Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Uttar Pradesh, Varanasi, India

de Carvalho Aguiar P.:
 Hospital Israelita Albert Einstein, São Paulo, Brazil

Damásio J.:
 Department of Neurology, Hospital de Santo António - Centro Hospitalar Universitário do Porto, Porto, Portugal

de Michele G.:
 Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy

De Rosa A.:
 Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy

Dorszewska J.:
 Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland

Ertan S.:
 Department of Neurology, School of Medicine, Koç University, Istanbul, Turkey

Fahn S.:
 Department of Neurology, Columbia University, New York, NY, United States

Farrer M.J.:
 Fixel Institute, Department of Neurology, University of Florida, Gainesville, FL, United States

Fedotova E.Y.:
 Department of Neurogenetics, Research Center of Neurology, Moscow, Russian Federation

Ferese R.:
 IRCCS Neuromed, Localita‘ Camerelle, Pozzilli, Isernia, Italy

Ferreira J.J.:
 Laboratory of Clinical Pharmacology and Therapeutics, University of Lisbon, Lisbon, Portugal

Foroud T.:
 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States

Funayama M.:
 Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo, Tokyo, Japan

Gagliardi M.:
 Institute of Biomedical Research and Innovation, National Research Council, Cosenza, Italy

Gambardella S.:
 IRCCS Neuromed, Localita‘ Camerelle, Pozzilli, Isernia, Italy

Garraux G.:
 Department of Neurology, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium

Garrido A.:
 Parkinson Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Barcelona, Spain

Gatto E.M.:
 Movement Disorders, Department of Neurology, Instituto de Neurosciencias Buenos Aires, Buenos Aires, Argentina

Genç G.:
 Department of Neurology, University of Health Sciences, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey

Giladi N.:
 Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel

Gómez-Garre P.:
 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Hanagasi H.:
 Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

Hattori N.:
 Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo, Tokyo, Japan

Hentati F.:
 Mongi Ben Hmida National Institute of Neurology, Tunis, Tunisia

Hertz J.M.:
 Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark

Illarioshkin S.N.:
 Department of Neurogenetics, Research Center of Neurology, Moscow, Russian Federation

Jankovic J.:
 Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States

Kasten M.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

 Department of Psychiatry and Psychotherapy and Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Kim Y.J.:
 Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea

Klein C.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Klivényi P.:
 Department of Neurology, University of Szeged, Szeged, Hungary

Kostic V.S.:
 Department for Neurodegeneration, Clinic for Neurology CCS, Belgrade, Serbia

Koziorowski D.:
 Department of Neurology, Medical University in Warsaw, Warsaw, Poland

Krüger R.:
 Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg

Kühn A.A.:
 Movement Disorder and Neuromodulation Unit, Charité, Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany

Kuhlenbäumer G.:
 Department of Neurology, Christian-Albrechts-Universität, Kiel, Germany

Kuo M.-C.:
 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Lang A.E.:
 Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada

Lee-Chen G.-J.:
 Department of Life Science, National Taiwan Normal University, Taipei, Taiwan

Lesage S.:
 Sorbonne University, Paris Brain Institute – ICM, Inserm, CNRS, Paris, France

Lim S.-Y.:
 Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Lin C.-H.:
 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Lohmann K.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Lynch T.:
 Department of Neurology, The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland

Marder K.:
 Department of Neurology, Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States

Markopoulou K.:
 Department of Neurology, NorthShore University HealthSystem, Evanston Illinois and Department of Neurology, University of Chicago, Chicago, IL, United States

Martikainen M.:
 Neurocenter, Turku University Hospital, Turku, Finland

Mellick G.D.:
 Griffith Institute for Drug Discovery (GRIDD), School of Environment and Science, Griffith University, Brisbane, QLD, Australia

Menéndez-González M.:
 Servicio Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain

Merello M.:
 Sección Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina

Mir P.:
 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

Mirelman A.:
 Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel

 Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel

Mollenhauer B.:
 Movement Disorder Paracelsus-Elena-Klinik, Kassel, Germany

Morgadinho A.:
 Movement Disorders Clinic, Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

Nishioka K.:
 Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan

Olszewska D.A.:
 Department of Neurology, The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland

Padmanabhan S.:
 Research Programs, The Michael J. Fox Foundation for Parkinson's Research, New York, NY, United States

Petrucci S.:
 Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy

Pimentel M.M.G.:
 Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil

Pulkes T.:
 Division of Neurology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Puschmann A.:
 Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden

Ran C.:
 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Riess O.:
 Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany

Ross O.A.:
 Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States

Rossi M.:
 Sección Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina

Sammler E.M.:
 Neurology Department, Ninewells Hospital and Medical School, Dundee, United Kingdom

Satake W.:
 Sección Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina

Saunders-Pullman R.:
 Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Schaake S.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Petersen M.S.:
 Centre of Health Science, University of the Faroe Islands, Tórshavn, Faroe Islands

Skorvanek M.:
 Department of Neurology, Pavol Jozef Šafárik University in Košice, Košice, Slovakia

Stefanis L.:
 First Department of Neurology, Medical School of the National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece

Spitz M.:
 Neurology Service, State University of Rio de Janeiro, Rio de Janeiro, Brazil

Suchowersky O.:
 Department of Medicine, Medical Genetics and Pediatrics, University of Alberta, Edmonton, AB, Canada

Sue C.M.:
 Department of Neurogenetics, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia

Tan A.H.:
 Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Tan E.-K.:
 Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore General Hospital, Singapore, Singapore

Thaler A.:
 Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel

 Movement Disorders, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel

Termsarasab P.:
 Division of Neurology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Tesson C.:
 Sorbonne University, Paris Brain Institute – ICM, Inserm, CNRS, Paris, France

Toda T.:
 Department of Neurology, The University of Tokyo, Tokyo, Japan

Toft M.:
 Department of Neurology, Oslo University Hospital, Oslo, Norway

Tolosa E.:
 Parkinson Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Barcelona, Spain

Torres-Ramirez L.:
 Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru

Tumas V.:
 Behavioral and Movement Disorders Section, Ribeirão Preto Medical School, University of São Paulo, Brazil

Valente E.M.:
 Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia

van de Warrenburg B.:
 Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Centre, Nijmegen, Netherlands

Vidailhet M.:
 Department of Neurology, Sorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France

Vollstedt E.-J.:
 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

Waters C.:
 Department of Neurology, Columbia University, New York, NY, United States

Williams-Gray C.H.:
 Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom

Winkelmann J.:
 Institute of Neurogenomics, Helmholtz Zentrum Muenchen, Neuherberg, Germany

Wu Y.-R.:
 Department of Neurology, Chang Gung University, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

Wurster I.:
 Department of Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Baden Wuerttemberg, Germany, Hertie Institute for Clinical Brain Research and German Centre for Neurodegenerative Diseases, Tuebingen, Germany

Wszolek Z.K.:
 Department of Neurology, Mayo Clinic, Jacksonville, FL, United States

Wu R.-M.:
 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Zhang B.-R.:
 Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

Zimprich A.:
 Department of Neurology, Medical University, Vienna, Austria
ISSN: 08853185
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 38 Número: 2
Páginas: 286-303
WOS Id: 000928274300001
ID de PubMed: 36692014
imagen Green Published, hybrid, All Open Access; Green

MÉTRICAS