Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1

Arch Cardiovasc Dis. 2013 Dec;106(12):635-43. doi: 10.1016/j.acvd.2013.08.003. Epub 2013 Oct 17.


Background: In patients with myotonic dystrophy type 1 (DM1), the mechanisms underlying sudden cardiac death, which occurs in up to 1/3 of patients, are unclear.

Aims: To study the potential role of Brugada syndrome in ventricular tachyarrhythmias and sudden death in DM1 patients.

Methods: We screened 914 adult patients included in the DM1 Heart Registry during 2000-2009 for the presence of type 1 Brugada pattern on electrocardiogram (ECG). We also performed direct sequencing of SCN5A in patients with Brugada pattern. Further, we analysed SCN5A splicing on ventricular myocardial specimens harvested during cardiac transplantation in a 45-year-old patient with DM1 and three controls with inherited dilated cardiomyopathy.

Results: A type 1 Brugada pattern was present on the ECG of seven of 914 patients (0.8%), including five with a history of sustained ventricular tachyarrhythmia or sudden death, who fulfilled the criteria for Brugada syndrome. SCN5A sequencing was normal in all patients. Ventricular myocardial specimen analysis displayed abnormal splicing of SCN5A exon 6, characterized by over-expression of the 'neonatal' isoform, called exon 6A, in the patient with DM1, but not from the controls.

Conclusion: Our findings suggest a potential implication of Brugada syndrome in sudden death in DM1, which may be related to missplicing of SCN5A. Our findings provide a new insight into the pathophysiology of heart disease in DM1.

Trial registration: NCT01136330.

Keywords: Alternative splicing; Brugada syndrome; Canal sodique cardiaque humain Na(v)1.5; Cardiac sodium channel Na(v)1.5; DM1; DMPK; DNA; Dystrophie myotonique de type 1; ECG; Human; Myotonic dystrophy type 1; PCR; RNA; RT; SCN5A; SD; Syndrome de Brugada; cDNA; complementary deoxyribonucleic acid; deoxyribonucleic acid; dystrophia myotonica protein kinase; dystrophia myotonica type 1; electrocardiogram; mRNA; messenger ribonucleic acid; polymerase chain reaction; reverse transcriptase; ribonucleic acid; standard deviation; Épissage alternatif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing*
  • Biopsy
  • Brugada Syndrome / diagnosis
  • Brugada Syndrome / genetics*
  • Brugada Syndrome / mortality
  • Case-Control Studies
  • DNA Mutational Analysis
  • Death, Sudden, Cardiac / epidemiology*
  • Electrocardiography
  • Exons
  • France / epidemiology
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Myotonic Dystrophy / diagnosis
  • Myotonic Dystrophy / genetics*
  • Myotonic Dystrophy / mortality
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Phenotype
  • Prevalence
  • Registries
  • Risk Factors
  • Young Adult


  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human

Associated data