Embracing Monogenic Parkinson's Disease: The <scp>MJFF</scp> Global Genetic <scp>PD</scp> Cohort-Reference-Cited by-同舟云学术

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

Published:2023-01-24 Issue:2 Volume:38 Page:286-303
ISSN:0885-3185
Container-title:Movement Disorders
language:en
Short-container-title:Movement Disorders

Author:

Vollstedt Eva‐Juliane¹^ORCID,Schaake Susen¹,Lohmann Katja¹^ORCID,Padmanabhan Shalini²,Brice Alexis³,Lesage Suzanne⁴,Tesson Christelle⁴,Vidailhet Marie³,Wurster Isabel⁵,Hentati Faycel⁶,Mirelman Anat⁷^ORCID,Giladi Nir⁸,Marder Karen⁹,Waters Cheryl¹⁰,Fahn Stanley¹⁰,Kasten Meike¹¹,Brüggemann Norbert¹²^ORCID,Borsche Max¹²^ORCID,Foroud Tatiana¹³,Tolosa Eduardo¹⁴^ORCID,Garrido Alicia¹⁴,Annesi Grazia¹⁵,Gagliardi Monica¹⁵,Bozi Maria¹⁶,Stefanis Leonidas¹⁷,Ferreira Joaquim J.¹⁸^ORCID,Correia Guedes Leonor¹⁹,Avenali Micol²⁰,Petrucci Simona²¹,Clark Lorraine²²,Fedotova Ekaterina Y.²³,Abramycheva Natalya Y.²³,Alvarez Victoria²⁴^ORCID,Menéndez‐González Manuel²⁵,Jesús Maestre Silvia²⁶,Gómez‐Garre Pilar²⁶,Mir Pablo²⁶^ORCID,Belin Andrea Carmine²⁷,Ran Caroline²⁷,Lin Chin‐Hsien²⁸,Kuo Ming‐Che²⁸^ORCID,Crosiers David²⁹,Wszolek Zbigniew K.³⁰,Ross Owen A.³¹^ORCID,Jankovic Joseph³²,Nishioka Kenya³³^ORCID,Funayama Manabu³⁴,Clarimon Jordi³⁵,Williams‐Gray Caroline H.³⁶^ORCID,Camacho Marta³⁶^ORCID,Cornejo‐Olivas Mario³⁷^ORCID,Torres‐Ramirez Luis³⁸,Wu Yih‐Ru³⁹^ORCID,Lee‐Chen Guey‐Jen⁴⁰,Morgadinho Ana⁴¹,Pulkes Teeratorn⁴²,Termsarasab Pichet⁴²^ORCID,Berg Daniela⁴³,Kuhlenbäumer Gregor⁴³,Kühn Andrea A.⁴⁴,Borngräber Friederike⁴⁴^ORCID,de Michele Giuseppe⁴⁵,De Rosa Anna⁴⁵,Zimprich Alexander⁴⁶^ORCID,Puschmann Andreas⁴⁷,Mellick George D.⁴⁸,Dorszewska Jolanta⁴⁹,Carr Jonathan⁵⁰,Ferese Rosangela⁵¹,Gambardella Stefano⁵¹^ORCID,Chase Bruce⁵²^ORCID,Markopoulou Katerina⁵³,Satake Wataru⁵⁴,Toda Tatsushi⁵⁵,Rossi Malco⁵⁴,Merello Marcelo⁵⁶,Lynch Timothy⁵⁷,Olszewska Diana A.⁵⁷^ORCID,Lim Shen‐Yang⁵⁸,Ahmad‐Annuar Azlina⁵⁹,Tan Ai Huey⁵⁸^ORCID,Al‐Mubarak Bashayer⁶⁰,Hanagasi Hasmet⁶¹,Koziorowski Dariusz⁶²,Ertan Sibel⁶³,Genç Gençer⁶⁴,de Carvalho Aguiar Patricia⁶⁵,Barkhuizen Melinda⁶⁶^ORCID,Pimentel Marcia M.G.⁶⁷,Saunders‐Pullman Rachel⁶⁸,van de Warrenburg Bart⁶⁹,Bressman Susan⁷⁰,Toft Mathias⁷¹,Appel‐Cresswell Silke⁷²^ORCID,Lang Anthony E.⁷³,Skorvanek Matej⁷⁴^ORCID,Boon Agnita J.W.⁷⁵,Krüger Rejko⁷⁶,Sammler Esther M.⁷⁷^ORCID,Tumas Vitor⁷⁸,Zhang Bao‐rong⁷⁹^ORCID,Garraux Gaetan⁸⁰,Chung Sun Ju⁸¹^ORCID,Kim Yun Joong⁸²,Winkelmann Juliane⁸³,Sue Carolyn M.⁸⁴,Tan Eng‐King⁸⁵,Damásio Joana⁸⁶,Klivényi Péter⁸⁷,Kostic Vladimir S.⁸⁸,Arkadir David⁸⁹,Martikainen Mika⁹⁰,Borges Vanderci⁹¹,Hertz Jens Michael⁹²,Brighina Laura⁹³,Spitz Mariana⁹⁴,Suchowersky Oksana⁹⁵,Riess Olaf⁹⁶,Das Parimal⁹⁷,Mollenhauer Brit⁹⁸,Gatto Emilia M.⁹⁹,Petersen Maria Skaalum¹⁰⁰,Hattori Nobutaka³⁴,Wu Ruey‐Meei²⁸,Illarioshkin Sergey N.²³,Valente Enza Maria¹⁰¹,Aasly Jan O.¹⁰²¹⁰³,Aasly Anna¹⁰⁴,Alcalay Roy N.¹⁰,Thaler Avner¹⁰⁵,Farrer Matthew J.¹⁰⁶,Brockmann Kathrin⁵,Corvol Jean‐Christophe¹⁰⁷,Klein Christine¹,

Affiliation:

1. Institute of Neurogenetics University of Lübeck Lübeck Germany

2. Research Programs The Michael J. Fox Foundation for Parkinson's Research New York New York USA

3. Department of Neurology Sorbonne University, Paris Brain Institute ‐ ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié‐Salpêtrière Hospital Paris France

4. Sorbonne University Paris Brain Institute – ICM, Inserm, CNRS Paris France

5. 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

6. Mongi Ben Hmida National Institute of Neurology Tunis Tunisia

7. Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel‐Aviv Medical Center, Tel‐Aviv, Israel; Sackler School of Medicine, Tel‐Aviv University, Tel‐Aviv, Israel; Sagol School of Neuroscience Tel‐Aviv University Tel‐Aviv Israel

8. Neurological Institute, Tel‐Aviv Medical Center, Tel‐Aviv, Israel; Sackler School of Medicine, Sagol School of Neuroscience Tel‐Aviv University Tel‐Aviv Israel

9. Department of Neurology, Taub Institute for Alzheimer's Disease and the Aging Brain Columbia University New York New York USA

10. Department of Neurology Columbia University New York New York USA

11. Department of Psychiatry and Psychotherapy and Institute of Neurogenetics University of Lübeck Lübeck Germany

12. Department of Neurology and Institute of Neurogenetics University of Lübeck Lübeck Germany

13. Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA

14. 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

15. Institute of Biomedical Research and Innovation National Research Council Cosenza Italy

16. Parkinson's and Movement Disorders Unit, 2nd Department of Neurology of the University of Athens Attikon Hospital, Haidari, Athens, Greece; Psychiatry Hospital of Attica "Dafni," Neurology Department, Haidari Athens Greece

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

18. Laboratory of Clinical Pharmacology and Therapeutics, University of Lisbon, Lisbon, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculty of Medicine University of Lisbon Lisbon Portugal

19. Department of Neuroscience and Mental Health, Neurology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Faculty of Medicine University of Lisbon Lisbon Portugal

20. Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioural Sciences University of Pavia Pavia Italy

21. Department of Clinical and Molecular Medicine Sapienza University of Rome, Rome, Italy; Sant' Andrea University Hospital Rome Italy

22. Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons Columbia University Irving Medical Center, New York, New York, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA; Laboratory of Personalized Genomic Medicine, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center New York New York USA

23. Department of Neurogenetics, Research Center of Neurology Moscow Russia

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

25. Servicio Neurología, Hospital Universitario Central de Asturias Oviedo, Spain; Instituto de Investigación; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) Oviedo Spain

26. 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; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain

27. Department of Neuroscience Karolinska Institutet Stockholm Sweden

28. Department of Neurology National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University College of Medicine Taipei Taiwan

29. Department of Neurology Antwerp University Hospital, Edegem, Belgium; Born Bunge Institute, Department of Neurology, University of Antwerp, Wilrijk, Belgium; Center for Molecular Neurology, VIB Wilrijk Belgium

30. Department of Neurology Mayo Clinic Jacksonville Florida USA

31. Department of Neuroscience Mayo Clinic Jacksonville Florida USA

32. Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology Baylor College of Medicine Houston Texas USA

33. Department of Neurology Juntendo University School of Medicine, Bunkyo Tokyo Japan

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

35. Department of Neurology, Biomedical Research Institute IIB‐Sant Pau Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain

36. Department of Clinical Neurosciences University of Cambridge Cambridge UK

37. Neurogenetics Research Center Instituto Nacional de Ciencias Neurologicas, Lima, Peru; Center for Global Health, Universidad Peruana Cayetano Heredia Lima Peru

38. Movement Disorders Unit Instituto Nacional de Ciencias Neurologicas Lima Peru

39. Department of Neurology Chang Gung University, Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan

40. Department of Life Science National Taiwan Normal University Taipei Taiwan

41. Movement Disorders Clinic, Department of Neurology Centro Hospitalar e Universitário de Coimbra Coimbra Portugal

42. Division of Neurology, Department of Medicine Ramathibodi Hospital, Mahidol University Bangkok Thailand

43. Department of Neurology Christian‐Albrechts‐Universität Kiel Germany

44. Movement Disorder and Neuromodulation Unit, Charité, Universitätsmedizin Berlin Department of Neurology Berlin Germany

45. Department of Neurosciences and Reproductive and Odontostomatological Sciences Federico II University Naples Italy

46. Department of Neurology Medical University Vienna Austria

47. Department of Neurology Clinical Sciences, Lund University, Lund, Sweden; Department of Neurology, Skåne University Lund Sweden

48. Griffith Institute for Drug Discovery (GRIDD) School of Environment and Science, Griffith University Brisbane Queensland Australia

49. Laboratory of Neurobiology, Department of Neurology Poznan University of Medical Sciences Poznan Poland

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

51. IRCCS Neuromed, Localita‘ Camerelle, Pozzilli, Isernia, Italy; Department of Biomolecular Sciences, University of Urbino “Carlo Bo” Urbino Italy

52. Department of Neurology NorthShore University HealthSystem Evanston Illinois USA

53. Department of Neurology NorthShore University HealthSystem, Evanston Illinois and Department of Neurology, University of Chicago Chicago Illinois USA

54. Sección Movimientos Anormales, Departamento de Neurociencias Fleni, Buenos Aires, Argentina; Argentine National Scientific and Technological Research Council (CONICET) Buenos Aires Argentina

55. Department of Neurology The University of Tokyo Tokyo Japan

56. Sección Movimientos Anormales, Departamento de Neurociencias Fleni, Buenos Aires, Argentina; Argentine National Scientific and Technological Research Council (CONICET), Argentina; Pontificia Universidad Católica Argentina (UCA) Buenos Aires Argentina

57. Department of Neurology The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Medical Sciences, University College Dublin Dublin Ireland

58. 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

59. Department of Biomedical Science Faculty of Medicine, University of Malaya Kuala Lumpur Malaysia

60. Behavioural Genetics Unit, Department of Genetics Research Centre, King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia

61. Department of Neurology Istanbul Faculty of Medicine, Istanbul University Istanbul Turkey

62. Department of Neurology Medical University in Warsaw Warsaw Poland

63. Department of Neurology School of Medicine, Koç University Istanbul Turkey

64. Department of Neurology University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital İstanbul Turkey

65. Hospital Israelita Albert Einstein São Paulo, Brazil; Department of Neurology and Neurosurgery, Universidade Federal de São Paulo São Paulo Brazil

66. DST/NWU Preclinical Drug Development Platform North‐West University Potchefstroom North‐West South Africa

67. Department of Genetics Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro Rio de Janeiro Brazil

68. Department of Neurology Icahn School of Medicine at Mount Sinai New York New York USA

69. Department of Neurology Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Centre Nijmegen The Netherlands

70. Department of Neurology Beth Israel Medical Center, New York, New York, USA; Department of Neurology at Albert Einstein College of Medicine New York New York USA

71. Department of Neurology Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo Oslo Norway

72. Pacific Parkinson's Research Centre Division of Neurology, Department of Medicine Vancouver British Columbia Canada

73. Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Department of Medicine University of Toronto, Toronto Western Hospital Toronto Ontario Canada

74. Department of Neurology Pavol Jozef Šafárik University in Košice, Košice, Slovakia; Department of Neurology, University Hospital L. Pasteur Kosice Slovakia

75. Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands

76. Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg, Esch‐sur‐Alzette, Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg; Parkinson Research Clinic, Centre Hospitalier de Luxembourg (CHL) Luxembourg Luxembourg

77. Neurology Department, Ninewells Hospital and Medical School Dundee, United Kingdom; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee Dundee UK

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

79. Department of Neurology Second Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou China

80. Department of Neurology Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium; MoVeRe Group, GIGA‐CRC In Vivo Imaging, University of Liege Liège Belgium

81. Medical Genetic Center, Department of Neurology Asan Medical Center, University of Ulsan College of Medicine Seoul South Korea

82. Department of Neurology Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology, Yongin Severance Hospital, Yonsei University Health System Yongin South Korea

83. Institute of Neurogenomics, Helmholtz Zentrum Muenchen, Neuherberg, Germany; Neurogenetics, Technische Universitaet Muenchen, Munich, Germany; Institute of Human Genetics, Klinikum rechts der Isar der TUM, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy) Munich Germany

84. Department of Neurogenetics Kolling Institute, University of Sydney, Sydney, New South Wales, Australia; Department of Neurology, Royal North Shore Hospital St Leonards New South Wales Australia

85. Department of Neurology National Neuroscience Institute, Duke NUS Medical School, Singapore General Hospital Singapore Singapore

86. Department of Neurology Hospital de Santo António ‐ Centro Hospitalar Universitário do Porto, Porto, Portugal; UnIGENe, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto Portugal

87. Department of Neurology University of Szeged Szeged Hungary

88. Department for Neurodegeneration Clinic for Neurology CCS Belgrade Serbia

89. Department of Neurology Hadassah Medical Center and the Hebrew University Jerusalem Israel

90. Neurocenter Turku University Hospital, Turku, Finland; Clinical Neurosciences, Faculty of Medicine, University of Turku Turku Finland

91. Department of Neurology and Neurosurgery Universidade Federal de São Paulo São Paulo Brazil

92. Department of Clinical Genetics Odense University Hospital Odense C Denmark

93. Department of Neurology Milan Center for Neuroscience, University of Milano‐Bicocca/San Gerardo Hospital Monza Italy

94. Neurology Service State University of Rio de Janeiro Rio de Janeiro Brazil

95. Department of Medicine, Medical Genetics and Pediatrics University of Alberta Edmonton Alberta Canada

96. Institute of Medical Genetics and Applied Genomics University of Tuebingen Tuebingen Germany

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

98. Movement Disorder Paracelsus‐Elena‐Klinik Kassel, Germany; Department of Neurology, University Medical Center Göttingen Göttingen Germany

99. Movement Disorders, Department of Neurology Instituto de Neurosciencias Buenos Aires Buenos Aires Argentina

100. Centre of Health Science University of the Faroe Islands, Tórshavn, Faroe Islands; Department of Occupational Medicine and Public Health, The Faroese Hospital System Tórshavn Faroe Islands

101. Neurogenetics Research Centre IRCCS Mondino Foundation, Pavia; Department of Molecular Medicine, University of Pavia Pavia Italy

102. Department of Neurology St. Olavs Hospital Trondheim Norway

103. Department of Neuroscience Norwegian University of Science and Technology Trondheim Norway

104. Department of Neuromedicine and Movement Science Norwegian University of Science and Technology Trondheim Norway

105. Movement Disorders, Neurological Institute Tel‐Aviv Medical Center, Tel‐Aviv, Israel; Sagol School of Neuroscience, Tel‐Aviv University, Tel‐Aviv, Israel; Sackler School of Medicine, Tel‐Aviv University Tel‐Aviv Israel

106. Fixel Institute, Department of Neurology University of Florida Gainesville Florida USA

107. Sorbonne University Paris Brain Institute ‐ ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié‐Salpêtrière Hospital, Department of Neurology Paris France

Abstract

AbstractBackgroundAs 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.ObjectiveThe 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.MethodsWe 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.ResultsWe 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.ConclusionsWithin 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.

Funder

Michael J. Fox Foundation

NIHR Cambridge Biomedical Research Centre

Publisher

Wiley

Subject

Neurology (clinical),Neurology

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mds.29288

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