title: Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de cardiologie, université Paris-Descartes, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Institut de myologie, université Pierre et Marie-Curie, hôpital Pitié-Salpêtrière, AP-HP, 75013 Paris, France. Electronic address: karim.wahbi@cch.aphp.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Wahbi
authors.forename: Vincent
authors.initials: V
authors.lastname: Algalarrondo
authors.forename: Henri Marc
authors.initials: HM
authors.lastname: Bécane
authors.forename: Véronique
authors.initials: V
authors.lastname: Fressart
authors.forename: Chérif
authors.initials: C
authors.lastname: Beldjord
authors.forename: Kamel
authors.initials: K
authors.lastname: Azibi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lazarus
authors.forename: Nawal
authors.initials: N
authors.lastname: Berber
authors.forename: Hélène
authors.initials: H
authors.lastname: Radvanyi-Hoffman
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.forename: Anthony
authors.initials: A
authors.lastname: Béhin
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforêt
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hatem
authors.forename: Denis
authors.initials: D
authors.lastname: Duboc
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D001706:Biopsy; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D004562:Electrocardiography; D005091:Exons; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D015995:Prevalence; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
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