UNLABELLED: Familial long QT syndrome (LQTS) and Brugada syndrome are two distinct human hereditary cardiac diseases known to cause ventricular tachyarrhythmias (torsade de pointes) and idiopathic ventricular fibrillation, respectively, which can both lead to sudden death. OBJECTIVE: In this study we have identified and electrophysiologically characterized, in patients having either LQTS or Brugada syndrome, three mutations in SCN5A (a cardiac sodium channel gene). METHOD: The mutant channels were expressed in a mammalian expression system and studied by means of the patch clamp technique. RESULTS: The R1512W mutation found in our first patient diagnosed with Brugada syndrome produced a slowing of both inactivation and recovery from inactivation. The R4132G mutation found in our second patient who also presented Brugada syndrome, resulted in no measurable sodium currents. Both Brugada syndrome patients showed ST segment elevation and right bundle-branch block, and had experienced syncopes. The E1784K mutation found in the LQTS showed a persistent inward sodium current, a hyperpolarized shift of the steady-sate inactivation and a faster recovery from inactivation. CONCLUSION: The different clinical manifestations of these three mutations most probably originate from the distinct electrophysiological abnormalities of the mutant cardiac sodium channels reported in this study.
UNLABELLED: Familial long QT syndrome (LQTS) and Brugada syndrome are two distinct human hereditary cardiac diseases known to cause ventricular tachyarrhythmias (torsade de pointes) and idiopathic ventricular fibrillation, respectively, which can both lead to sudden death. OBJECTIVE: In this study we have identified and electrophysiologically characterized, in patients having either LQTS or Brugada syndrome, three mutations in SCN5A (a cardiac sodium channel gene). METHOD: The mutant channels were expressed in a mammalian expression system and studied by means of the patch clamp technique. RESULTS: The R1512W mutation found in our first patient diagnosed with Brugada syndrome produced a slowing of both inactivation and recovery from inactivation. The R4132G mutation found in our second patient who also presented Brugada syndrome, resulted in no measurable sodium currents. Both Brugada syndromepatients showed ST segment elevation and right bundle-branch block, and had experienced syncopes. The E1784K mutation found in the LQTS showed a persistent inward sodium current, a hyperpolarized shift of the steady-sate inactivation and a faster recovery from inactivation. CONCLUSION: The different clinical manifestations of these three mutations most probably originate from the distinct electrophysiological abnormalities of the mutant cardiac sodium channels reported in this study.
Authors: Hai Huang; Silvia G Priori; Carlo Napolitano; Michael E O'Leary; Mohamed Chahine Journal: Am J Physiol Heart Circ Physiol Date: 2010-11-12 Impact factor: 4.733
Authors: Kathryn E Mangold; Brittany D Brumback; Paweorn Angsutararux; Taylor L Voelker; Wandi Zhu; Po Wei Kang; Jonathan D Moreno; Jonathan R Silva Journal: Channels (Austin) Date: 2017-09-21 Impact factor: 2.581
Authors: Dan Hu; Hector Barajas-Martínez; Andre Terzic; Sungjo Park; Ryan Pfeiffer; Elena Burashnikov; Yuesheng Wu; Martin Borggrefe; Christian Veltmann; Rainer Schimpf; John J Cai; Gi-Byong Nam; Pramod Deshmukh; Melvin Scheinman; Mark Preminger; Jonathan Steinberg; Angélica López-Izquierdo; Daniela Ponce-Balbuena; Christian Wolpert; Michel Haïssaguerre; José Antonio Sánchez-Chapula; Charles Antzelevitch Journal: Int J Cardiol Date: 2014-01-04 Impact factor: 4.164
Authors: Lia Crotti; Cherisse A Marcou; David J Tester; Silvia Castelletti; John R Giudicessi; Margherita Torchio; Argelia Medeiros-Domingo; Savastano Simone; Melissa L Will; Federica Dagradi; Peter J Schwartz; Michael J Ackerman Journal: J Am Coll Cardiol Date: 2012-07-25 Impact factor: 24.094