Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

Publication Type:

Journal Article


Cardiovasc Res, Volume 46, Issue 1, p.55-65 (2000)


Adult, Bundle-Branch Block, Child, Death, Sudden, Cardiac, Electrocardiography, Female, Humans, Long QT Syndrome, Male, Mutation, Missense, NAV1.5 Voltage-Gated Sodium Channel, Patch-Clamp Techniques, Polymorphism, Single-Stranded Conformational, Sodium Channels, Syncope, Vasovagal, Syndrome


<p><b>UNLABELLED: </b>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.</p><p><b>OBJECTIVE: </b>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).</p><p><b>METHOD: </b>The mutant channels were expressed in a mammalian expression system and studied by means of the patch clamp technique.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p>

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