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SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.
Baruteau, Alban-Elouen; Kyndt, Florence; Behr, Elijah R; Vink, Arja S; Lachaud, Matthias; Joong, Anna; Schott, Jean-Jacques; Horie, Minoru; Denjoy, Isabelle; Crotti, Lia; Shimizu, Wataru; Bos, Johan M; Stephenson, Elizabeth A; Wong, Leonie; Abrams, Dominic J; Davis, Andrew M; Winbo, Annika; Dubin, Anne M; Sanatani, Shubhayan; Liberman, Leonardo; Kaski, Juan Pablo; Rudic, Boris; Kwok, Sit Yee; Rieubland, Claudine; Tfelt-Hansen, Jacob; Van Hare, George F; Guyomarc'h-Delasalle, Béatrice; Blom, Nico A; Wijeyeratne, Yanushi D; Gourraud, Jean-Baptiste; Le Marec, Hervé; Ozawa, Junichi; Fressart, Véronique; Lupoglazoff, Jean-Marc; Dagradi, Federica; Spazzolini, Carla; Aiba, Takeshi; Tester, David J; Zahavich, Laura A; Beauséjour-Ladouceur, Virginie; Jadhav, Mangesh; Skinner, Jonathan R; Franciosi, Sonia; Krahn, Andrew D; Abdelsayed, Mena; Ruben, Peter C; Yung, Tak-Cheung; Ackerman, Michael J; Wilde, Arthur A; Schwartz, Peter J.
Afiliación
  • Baruteau AE; Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
  • Kyndt F; Department of Congenital Cardiology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Behr ER; M3C CHU de Nantes, Fédération des Cardiopathies Congénitales, Nantes, F-44000, France.
  • Vink AS; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Lachaud M; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Joong A; Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
  • Schott JJ; Department of Pediatric Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
  • Horie M; Department of Clinical and Experimental Cardiology, Heart Centre, Academic Medical Center, Amsterdam, The Netherlands.
  • Denjoy I; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Crotti L; Division of Pediatric Cardiology, Morgan Stanley Children's Hospital, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA.
  • Shimizu W; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Bos JM; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Sciences, Otsu, Japan.
  • Stephenson EA; AP-HP, Ho
  • Wong L; Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milano, Italy.
  • Abrams DJ; Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
  • Davis AM; Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan.
  • Winbo A; Division of Heart Rhythm Services, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
  • Dubin AM; Division of Pediatric Cardiology, Department of Pediatrics, Mayo Clinic, Rochester, MN, USA.
  • Sanatani S; Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.
  • Liberman L; The Hospital for Sick Children, Labbatt Family, Heart Centre, University of Toronto, Toronto, Canada.
  • Kaski JP; Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
  • Rudic B; Inherited Cardiac Arrhythmia Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kwok SY; Department of Cardiology, The Royal Children's Hospital, Melbourne, Australia.
  • Rieubland C; Murdoch Children's Research Institute and University of Melbourne, Melbourne, Australia.
  • Tfelt-Hansen J; Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
  • Van Hare GF; Department of Congenital Cardiology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Guyomarc'h-Delasalle B; Greenlane Paediatric and Congenital Cardiac Services, Starship Childrens Hospital, Auckland, New Zealand.
  • Blom NA; Division of Pediatric Electrophysiology, Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA.
  • Wijeyeratne YD; Divisions of Cardiology, Department of Pediatrics and Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
  • Gourraud JB; Division of Pediatric Cardiology, Morgan Stanley Children's Hospital, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA.
  • Le Marec H; Department of Cardiology, Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital for Children, London, UK.
  • Ozawa J; Institute of Cardiovascular Science, University College London, London, UK.
  • Fressart V; Medical Faculty Mannheim of the University of Heidelberg, 1st Department of Medicine, Mannheim, Germany.
  • Lupoglazoff JM; DZHK (German Centre for Cardiovascular Research), Mannheim, Germany.
  • Dagradi F; Department of Paediatric Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
  • Spazzolini C; Division of Human Genetics, Department of Pediatrics, Inselspital, University of Bern, Switzerland.
  • Aiba T; Faculty of Health and Medical Science, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Tester DJ; Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Denmark.
  • Zahavich LA; Division of Cardiology, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
  • Beauséjour-Ladouceur V; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Jadhav M; Department of Pediatric Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
  • Skinner JR; Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK.
  • Franciosi S; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Krahn AD; L'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
  • Abdelsayed M; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Sciences, Otsu, Japan.
  • Ruben PC; AP-HP, Hôpital Pitié Salpétrière, Service de Biologie Moléculaire, Paris, France.
  • Yung TC; AP-HP, Hôpital Robert Debré, Service de Cardiologie Pédiatrique, Paris, France.
  • Ackerman MJ; Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milano, Italy.
  • Wilde AA; Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milano, Italy.
  • Schwartz PJ; Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Eur Heart J ; 39(31): 2879-2887, 2018 08 14.
Article en En | MEDLINE | ID: mdl-30059973
Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE. Conclusion: In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estudios de Asociación Genética / Canal de Sodio Activado por Voltaje NAV1.5 / Trastorno del Sistema de Conducción Cardíaco Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Eur Heart J Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estudios de Asociación Genética / Canal de Sodio Activado por Voltaje NAV1.5 / Trastorno del Sistema de Conducción Cardíaco Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Eur Heart J Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido