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
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