ArticleCardiovascular research2017
Multilevel analyses of SCN5A mutations in arrhythmogenic right ventricular dysplasia/cardiomyopathy suggest non-canonical mechanisms for disease pathogenesis.
Erratum issuedOpen access · bronzeAbstract readMulticenter StudyValidation Study
In one paragraph
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 102 papers.
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102citing papers in PubMed
14.1field-weighted citation impact, top 1% of its field
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Who cites it
102 citing papers in PubMed, 169 citations in OpenAlex.
- International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework.Circulation. Genomic and precision medicine · 2021Trial
- Pediatric dilated cardiomyopathy and the progression to heart failure: mechanisms and interventions focusing on the "gene-inflammation-metabolism" axis.Frontiers in cardiovascular medicine · 2026Review
- Ion channels and cardiac disease: mechanisms and functions of a disintegrin and metalloproteases and their substrates.Frontiers in cell and developmental biology · 2026Review
- Atrial Dilated Cardiomyopathy: From Molecular Pathogenesis to Clinical Implications.Journal of clinical medicine · 2025Review
- Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- SCN5A Cardiomyopathy: from Ion Channel Dysfunction To Clinical Disease.Current cardiology reports · 2025Review
- Advances in human induced pluripotent stem cell (hiPSC)-based disease modelling in cardiogenetics.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy.International journal of molecular sciences · 2025Review
- Characterization of a novel SCN5A mutation associated with long QT syndrome and arrhythmogenic right ventricular cardiomyopathy in a family.Forensic science, medicine, and pathology · 2025Article
- Pathophysiology of dilated cardiomyopathy: from mechanisms to precision medicine.Nature reviews. Cardiology · 2025Review
- Arrhythmogenic Right Ventricular Cardiomyopathy: A Comprehensive Review.Journal of cardiovascular development and disease · 2025Review
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Genetic background determines the severity of age-dependent cardiac structural abnormalities and arrhythmia susceptibility in Scn5a-1798insD mice.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Arrhythmogenic Left Ventricular Cardiomyopathy: From Diagnosis to Risk Management.Journal of clinical medicine · 2024Review
- In silico validation revealed the role of SCN5A mutations and their genotype-phenotype correlations in Brugada syndrome.Molecular genetics & genomic medicine · 2023Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Desmosomal Arrhythmogenic Cardiomyopathy: The Story Telling of a Genetically Determined Heart Muscle Disease.Biomedicines · 2023Review
- Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis.Cardiovascular research · 2023Article
- Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation.Circulation · 2023Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
32 authors at 12 institutions in 4 countries.
Anneline S J M Te RieleDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Esperanza Agullo-PascualLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Cynthia A JamesDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Alejandra Leo-MaciasLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Marina CerroneLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Mingliang ZhangLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Xianming LinLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Bin LinLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Nara L SobreiraMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, USA.
Nuria Amat-AlarconDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Roos F MarsmanHeart Centre, Department of Clinical and Experimental Cardiology, Academic Medical Center, Meibergdreef 9, Amsterdam, the Netherlands.
Brittney MurrayDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Crystal TichnellDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Jeroen F van der HeijdenDivision of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
Dennis DooijesDepartment of Medical Genetics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
Toon A B van VeenDepartment of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Yalelaan 50, Utrecht, the Netherlands.
Harikrishna TandriDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Steven J FowlerLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Richard N W HauerDivision of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the Netherlands.
Gordon TomaselliDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
Maarten P van den BergDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Matthew R G TaylorCardiovascular Institute and Adult Medical Genetics, University of Colorado Denver, 12605 E 16th Avenue, Aurora, CO, USA.
Francesca BrunCardiovascular Department, Ospedali Riuniti and University of Trieste, Via Farneto 3, Trieste, Italy.
Gianfranco SinagraCardiovascular Department, Ospedali Riuniti and University of Trieste, Via Farneto 3, Trieste, Italy.
Arthur A M WildeHeart Centre, Department of Clinical and Experimental Cardiology, Academic Medical Center, Meibergdreef 9, Amsterdam, the Netherlands.
Luisa MestroniCardiovascular Institute and Adult Medical Genetics, University of Colorado Denver, 12605 E 16th Avenue, Aurora, CO, USA.
Connie R BezzinaHeart Centre, Department of Clinical and Experimental Cardiology, Academic Medical Center, Meibergdreef 9, Amsterdam, the Netherlands.
Hugh CalkinsDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA.
J Peter van TintelenDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Lei BuLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Mario DelmarLeon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, NY, USA.
Daniel P JudgeDepartment of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, USA; djudge@jhmi.edu mario.delmar@nyumc.org lei.bu@med.nyu.edu.
New York University · USJohns Hopkins University · USJohns Hopkins Medicine · USAcademic Medical Center · NLUniversity Medical Center Utrecht · NLUniversity of Colorado Denver · USUniversity of Groningen · NLAzienda Sanitaria Universitaria Integrata di Trieste · ITHeidelberg University · DENetherlands Heart Institute · NLUniversity of Trieste · ITUtrecht University · NL
Funding
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MColorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0MBaylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6MGenetics, Mechanisms and Clinical Phenotypes of Arrhythmogenic CardiomyopathyR01HL116906 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI MARCUS, FRANK I, MESTRONI, LUISA · 2013 to 2016
$9.2MPH REGULATION OF CONNEXIN43--INTERMEDIARY STEPSR01GM057691 · NIGMS · UPSTATE MEDICAL UNIVERSITY · PI DELMAR, MARIO · 1999 to 2016
$5.6MRole of Desmosomes in Cardiac Electrical FunctionR01HL106632 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DELMAR, MARIO · 2011 to 2015
$2.8MMolecular Epidemiology of Dilated CardiomyopathR01HL069071 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MESTRONI, LUISA · 2002 to 2005
$2.3MWhole genome DNA sequencing to identify novel genes in dilated cardiomyopathyR01HL109209 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI TAYLOR, MATTHEW R · 2012 to 2016
$2.1MCardiomyocyte phenotype and mechanotransduction in Filamin C gene variants causing arrhythmogenic cardiomyopathyR01HL147064 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MESTRONI, LUISA, TAYLOR, MATTHEW R · 2020 to 2023
$2.1MNCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001082NCRR NIH HHS UL1 RR025780NHGRI NIH HHS U54 HG006542NHLBI NIH HHS R01 HL069071NHLBI NIH HHS R01 HL106632NHLBI NIH HHS R01 HL109209NHLBI NIH HHS R01 HL116906NHLBI NIH HHS R01 HL147064NIGMS NIH HHS R01 GM057691
Abstract
aimsArrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is often associated with desmosomal mutations. Recent studies suggest an interaction between the desmosome and sodium channel protein Na METHODS AND
resultsWe performed whole-exome sequencing in six ARVD/C patients (33% male, 38.2 ± 12.1 years) without a desmosomal mutation. We found a rare missense variant (p.Arg1898His; R1898H) in SCN5A in one patient. We generated induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CMs) from the patient's peripheral blood mononuclear cells. The variant was then corrected (R1898R) using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 technology, allowing us to study the impact of the R1898H substitution in the same cellular background. Whole-cell patch clamping revealed a 36% reduction in peak sodium current (P = 0.002); super-resolution fluorescence microscopy showed reduced abundance of Na
conclusionsAlmost 2% of ARVD/C patients harbour rare SCN5A variants. For one of these variants, we demonstrated reduced sodium current, Na
Indexed as
Mutation, MissenseAdultAntigens, CDArrhythmogenic Right Ventricular DysplasiaCadherinsCell DifferentiationCRISPR-Cas SystemsDNA Mutational AnalysisElectrocardiographyExomeFemaleGene EditingGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHEK293 CellsAntigens, CDCadherinsCDH2 protein, humanNAV1.5 Voltage-Gated Sodium ChannelSCN5A protein, humanSodiumArrhythmogenic right ventricular cardiomyopathyCardiomyopathyGeneticsIon channel electrophysiologySCN5A
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