Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
Por:
Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, Amin AS, Nannenberg EA, Ware JS, Whiffin N, Mazzarotto F, Škoric-Milosavljevic D, Krijger C, Arbelo E, Babuty D, Barajas-Martinez H, Beckmann BM, Bézieau S, Bos JM, Breckpot J, Campuzano O, Castelletti S, Celen C, Clauss S, Corveleyn A, Crotti L, Dagradi F, de Asmundis C, Denjoy I, Dittmann S, Ellinor PT, Ortuño CG, Giustetto C, Gourraud JB, Hazeki D, Horie M, Ishikawa T, Itoh H, Kaneko Y, Kanters JK, Kimoto H, Kotta MC, Krapels IPC, Kurabayashi M, Lazarte J, Leenhardt A, Loeys BL, Lundin C, Makiyama T, Mansourati J, Martins RP, Mazzanti A, Mörner S, Napolitano C, Ohkubo K, Papadakis M, Rudic B, Molina MS, Sacher F, Sahin H, Sarquella-Brugada G, Sebastiano R, Sharma S, Sheppard MN, Shimamoto K, Shoemaker MB, Stallmeyer B, Steinfurt J, Tanaka Y, Tester DJ, Usuda K, van der Zwaag PA, Van Dooren S, Van Laer L, Winbo A, Winkel BG, Yamagata K, Zumhagen S, Volders PGA, Lubitz SA, Antzelevitch C, Platonov PG, Odening KE, Roden DM, Roberts JD, Skinner JR, Tfelt-Hansen J, van den Berg MP, Olesen MS, Lambiase PD, Borggrefe M, Hayashi K, Rydberg A, Nakajima T, Yoshinaga M, Saenen JB, Kääb S, Brugada P, Robyns T, Giachino DF, Ackerman MJ, Brugada R, Brugada-Terradellas J, Gimeno JR, Hasdemir C, Guicheney P, Priori SG, Schulze-Bahr E, Makita N, Schwartz PJ, Shimizu W, Aiba T, Schott JJ, Redon R, Ohno S, Probst V, Behr ER, Barc J, Bezzina CR and Nantes Referral Center for inherited cardiac arrhythmia
Publicada:
1 ene 2021
Ahead of Print:
1 sep 2020
Resumen:
Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.
Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.
Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.
Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
Filiaciones:
Walsh R:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.
Lahrouchi N:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Tadros R:
Department of Medicine, Cardiovascular Genetics Center, Montreal Heart Institute and Faculty of Medicine, Université de Montréal, Montreal, QC, Canada
Kyndt F:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Glinge C:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Postema PG:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Amin AS:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Nannenberg EA:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Ware JS:
National Heart and Lung Institute, Imperial College London, London, United Kingdom
Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom
Whiffin N:
National Heart and Lung Institute, Imperial College London, London, United Kingdom
Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
MRC London Institute of Medical Sciences, Imperial College London, London, United Kingdom
Mazzarotto F:
National Heart and Lung Institute, Imperial College London, London, United Kingdom
Cardiovascular Research Centre, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Škoric-Milosavljevic D:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Krijger C:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Arbelo E:
Arrhythmia Section, Cardiology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
IDIBAPS, Institut d'Investigació August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Babuty D:
CHU Tours, Service de Cardiologie, Tours, France
Barajas-Martinez H:
Lankenau Institute for Medical Research, Wynnewood, PA, USA
Beckmann BM:
Department of Internal Medicine I, LMU Klinikum, Klinikum der Ludwig Maximilians Universität München, München, Germany
Bézieau S:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Bos JM:
Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, MN, USA
Breckpot J:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium
Campuzano O:
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain
Medical Science Department, School of Medicine, University of Girona, Girona, Spain
Biochemistry and Molecular Genetics Department, Hospital Clinic, University of Barcelona-IDIBAPS, Barcelona, Spain
Castelletti S:
Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Celen C:
Department of Cardiology, Ege University School of Medicine, Izmir, Turkey
Clauss S:
Department of Internal Medicine I, LMU Klinikum, Klinikum der Ludwig Maximilians Universität München, München, Germany
German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany
Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians University Munich (LMU), Munich, Germany
Corveleyn A:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
Crotti L:
Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
Istituto Auxologico Italiano, IRCCS-Laboratory of Cardiovascular Genetics, Cusano Milanino, MI, Italy
Dagradi F:
Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
de Asmundis C:
Heart Rhythm Management Center, Postgraduate program in Cardiac Electrophysiology and Pacing Universitair Ziekenhuis, Brussel-Vrije Universiteit Brussel, ERN Heart Guard Center, Brussels, Belgium
Denjoy I:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat, Université de Paris, Paris, France
AP-HP, Service de Cardiologie, Hôpital Bichat, Paris, France
Dittmann S:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany
Ellinor PT:
Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
Cardiovascular Disease Initiative, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
Ortuño CG:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Cardiogenetic Laboratory, Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca-IMIB, Murcia, Spain
Giustetto C:
Division of Cardiology, University of Torino, Department of Medical Sciences, "Città della Salute e della Scienza" Hospital, Torino, Italy
Gourraud JB:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Hazeki D:
Department of Pediatrics, Kagoshima City Hospital, Kagoshima, Japan
Horie M:
Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Japan
Ishikawa T:
Omics Research Center, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Itoh H:
Division of Patient Safety, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan
Kaneko Y:
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
Kanters JK:
Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Kimoto H:
Department of Molecular Physiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Kotta MC:
Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Istituto Auxologico Italiano, IRCCS-Laboratory of Cardiovascular Genetics, Cusano Milanino, MI, Italy
Krapels IPC:
Department of Clinical Genetics, Maastricht University Medical Center+, Maastricht, Netherlands
Kurabayashi M:
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
Lazarte J:
Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
Leenhardt A:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
CNMR Maladies Cardiaques Héréditaires Rares, Hôpital Bichat, Université de Paris, Paris, France
AP-HP, Service de Cardiologie, Hôpital Bichat, Paris, France
Loeys BL:
Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
Lundin C:
Department of Clinical Genetics and Pathology, Lund University, Lund, Sweden
Makiyama T:
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Mansourati J:
CHU Brest, Service de Cardiologie, Brest, France
Martins RP:
Univ Rennes, CHU Rennes, INSERM, Rennes, France
Mazzanti A:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy
Mörner S:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Centre for Cardiovascular Genetics, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
Napolitano C:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy
Ohkubo K:
Department of Cardiovascular Medicine, Nihon University, Tokyo, Japan
Papadakis M:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom
Cardiology Clinical Academic Group, St. George's University Hospitals' NHS Foundation Trust, London, United Kingdom
Rudic B:
Department of Medicine, University Medical Center Mannheim, Mannheim, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany
Molina MS:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Cardiogenetic Laboratory, Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca-IMIB, Murcia, Spain
Sacher F:
Hôpital Cardiologique du Haut-Lévêque, LIRYC Institute, Université Bordeaux, Bordeaux, France
Sahin H:
Department of Cardiology, Ege University School of Medicine, Izmir, Turkey
Sarquella-Brugada G:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Medical Science Department, School of Medicine, University of Girona, Girona, Spain
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Sebastiano R:
Medical Genetics, San Luigi Univesity Hospital, Orbassano, TO, Italy
Sharma S:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom
Cardiology Clinical Academic Group, St. George's University Hospitals' NHS Foundation Trust, London, United Kingdom
Sheppard MN:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom
Cardiology Clinical Academic Group, St. George's University Hospitals' NHS Foundation Trust, London, United Kingdom
Shimamoto K:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Shoemaker MB:
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Stallmeyer B:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany
Steinfurt J:
Department of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Freiburg, Germany
Tanaka Y:
Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
Tester DJ:
Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, MN, USA
Usuda K:
Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
van der Zwaag PA:
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Van Dooren S:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Centre for Medical Genetics, research group Reproduction and Genetics, research cluster Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
Van Laer L:
Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
Winbo A:
Department of Physiology, University of Auckland, Auckland, New Zealand
Winkel BG:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Yamagata K:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Zumhagen S:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany
Volders PGA:
Department of Cardiology, CARIM, Maastricht University Medical Center+, Maastricht, Netherlands
Lubitz SA:
Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
Cardiovascular Disease Initiative, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA
Antzelevitch C:
Lankenau Institute for Medical Research, Wynnewood, PA, USA
Platonov PG:
Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden
Odening KE:
Department of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Freiburg, Germany
Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Roden DM:
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA
Roberts JD:
Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, ON, Canada
Skinner JR:
Cardiac Inherited Disease Group, Starship Childrens Hospital, Auckland, New Zealand
Tfelt-Hansen J:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark
van den Berg MP:
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Olesen MS:
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Lambiase PD:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Barts Heart Centre, Barts Health NHS Trust & Institute of Cardiovascular Science, University College London, London, United Kingdom
Borggrefe M:
Department of Medicine, University Medical Center Mannheim, Mannheim, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany
Hayashi K:
Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
Rydberg A:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden
Nakajima T:
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
Yoshinaga M:
Department of Pediatrics, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
Saenen JB:
Department of Cardiology, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium
Kääb S:
Department of Internal Medicine I, LMU Klinikum, Klinikum der Ludwig Maximilians Universität München, München, Germany
German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany
Brugada P:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Heart Rhythm Management Center, UZ Brussel-VUB, Brussels, Belgium
Robyns T:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium
Giachino DF:
Medical Genetics, San Luigi Univesity Hospital, Orbassano, TO, Italy
Medical Genetics Department, Clinical and Biological Sciences, Univestity of Torino, Orbassano, TO, Italy
Ackerman MJ:
Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, Rochester, MN, USA
Brugada R:
Hospital Trueta, CiberCV, University of Girona, IDIBGI, Girona, Spain
Brugada-Terradellas J:
Cardiovascular Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
Gimeno JR:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Inherited Cardiac Disease Unit, Cardiology Department, University Hospital Virgen de la Arrixaca, Murcia, Spain
Hasdemir C:
Department of Cardiology, Ege University School of Medicine, Izmir, Turkey
Guicheney P:
INSERM, Sorbonne University, UMRS 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
Priori SG:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy
Schulze-Bahr E:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Institute for Genetics of Heart Diseases, University Hospital Münster, Münster, Germany
Makita N:
Omics Research Center, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Schwartz PJ:
Istituto Auxologico Italiano, IRCCS-Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Istituto Auxologico Italiano, IRCCS-Laboratory of Cardiovascular Genetics, Cusano Milanino, MI, Italy
Shimizu W:
Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
Aiba T:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Schott JJ:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Redon R:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Ohno S:
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Japan
Probst V:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Behr ER:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom
Cardiology Clinical Academic Group, St. George's University Hospitals' NHS Foundation Trust, London, United Kingdom
Barc J:
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Université de Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
Bezzina CR:
Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands
Green Submitted, Green Accepted, Bronze
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