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.
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 DM1patients. 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.
Authors: Véronique Bissay; Sophie C H Van Malderen; Kathelijn Keymolen; Willy Lissens; Uschi Peeters; Dorien Daneels; Anna C Jansen; Gudrun Pappaert; Pedro Brugada; Jacques De Keyser; Sonia Van Dooren Journal: Eur J Hum Genet Date: 2015-06-03 Impact factor: 4.246
Authors: Eric T Wang; J Matthew Taliaferro; Ji-Ann Lee; Indulekha P Sudhakaran; Wilfried Rossoll; Christina Gross; Kathryn R Moss; Gary J Bassell Journal: J Neurosci Date: 2016-11-09 Impact factor: 6.167
Authors: Matteo D'Antonio; Jennifer P Nguyen; Timothy D Arthur; Hiroko Matsui; Margaret K R Donovan; Agnieszka D'Antonio-Chronowska; Kelly A Frazer Journal: PLoS Comput Biol Date: 2022-02-28 Impact factor: 4.475
Authors: Donald M Dixon; Jongkyu Choi; Ayea El-Ghazali; Sun Young Park; Kenneth P Roos; Maria C Jordan; Michael C Fishbein; Lucio Comai; Sita Reddy Journal: Sci Rep Date: 2015-03-12 Impact factor: 4.379