Genetic arrhythmias complicating patients with dilated cardiomyopathy: How it happens

  • Jeffrey A. Towbin
    Address reprint requests and correspondence: Dr Jeffrey A. Towbin, Heart Institute, Division of Pediatric Cardiology, Le Bonheur Children’s Hospital, 49 N. Dunlap St, FOB, Room 344, Memphis, TN 38103.
    Heart Institute, Division of Pediatric Cardiology, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, Tennessee
    Search for articles by this author
Published:October 18, 2019DOI:
      In this edition of Heart Rhythm Journal, Li et al
      • Li Z.
      • Chen P.
      • Li C.
      • et al.
      Genetic arrhythmias complicating patients with dilated cardiomyopathy.
      report on patients with dilated cardiomyopathy (DCM) and arrhythmias (DCM-A) compared to patients with DCM with no arrhythmias (DCM-NA), with the explicit intent to identify the genetic causes of arrhythmias in DCM. Using whole-exome sequencing and high-depth targeted next-generation sequencing followed by Sanger sequencing of all causative variants to eliminate false-positive results, 8 specific DCM-A pedigrees and 2 separate cohorts of 1232 consecutive unrelated sporadic DCM-NA patients were studied (550 patients in discovery cohort; 682 patients in replication cohort). Of these patients, 470 had DCM-A (250 in discovery cohort; 220 in replication cohort) and 762 had DCM-NA (300 in discovery cohort; 462 in replication cohort). Pathogenic variants were identified in genes known to cause long QT syndrome (LQTS) that independently co-segregated in 2 unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes were identified in 4.9% of sporadic DCM-A patients (4.0% in discovery cohort; 5.9% in replication cohort) but in only 0.1% of sporadic DCM-NA patients. These arrhythmia-related pathogenic variants included those resulting in LQTS, atrial fibrillation (AF), sick sinus syndrome (SSS), cardiac conduction disease (CCD), and Brugada syndrome (BrS). The authors concluded that some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants in ion channel-encoding genes.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Heart Rhythm
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Li Z.
        • Chen P.
        • Li C.
        • et al.
        Genetic arrhythmias complicating patients with dilated cardiomyopathy.
        Heart Rhythm. 2020; 17: 305-312
        • Leyva-Leyva M.
        • Sandoval A.
        • Felix R.
        • González-Ramírez R.
        Biochemical and functional interplay between ion channels and the components of the dystrophin-associated glycoprotein complex.
        J Membr Biol. 2018; 251: 535-550
        • Tsubata S.
        • Bowles K.R.
        • Vatta M.
        • et al.
        Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy.
        J Clin Invest. 2000; 106: 655-662
        • Heydemann A.
        • Demonbreun A.
        • Hadhazy M.
        • Earley J.U.
        • McNally E.M.
        Nuclear sequestration of δ-sarcoglycan disrupts the nuclear localization of lamin A/C and emerin in cardiomyocytes.
        Hum Mol Genet. 2007; 16: 355-363
        • Towbin J.A.
        • McKenna W.J.
        • Abrams D.J.
        • et al.
        2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
        Heart Rhythm. 2019; 16: e373-e409
        • Hershberger R.E.
        • Renato Pinto J.
        • Parks S.B.
        • et al.
        Clinical and functional characterization of TNNT2 mutations identified in patients with dilated cardiomyopathy.
        Circ Cardiovasc Genet. 2009; 2: 306-313
        • Clippinger S.R.
        • Cloonan P.E.
        • Greenberg L.
        • et al.
        Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy.
        Proc Natl Acad Sci U S A. 2019; 116: 17831-17840
        • Deo M.
        • Ruan Y.
        • Pandit S.V.
        • et al.
        KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia.
        Proc Natl Acad Sci U S A. 2013; 110: 4291-4296
        • Bianchi B.
        • Ozhathil L.C.
        • Medeiros-Domingo A.
        • Gollob M.H.
        • Abriel H.
        Four TRPM4 cation channel mutations found in cardiac conduction diseases lead to altered protein stability.
        Front Physiol. 2018; 9: 177

      Linked Article