A newly characterized SCN5A mutation underlying Brugada syndrome unmasked by hyperthermia

Ngai Shing Mok, Silvia G. Priori, Carlo Napolitano, Ngai Yin Chan, Mohamed Chahine, Ghayath Baroudi

Research output: Contribution to journalArticle

Abstract

Febrile illness has been rarely reported to modulate ST segment elevation in right precordial leads on ECG or even precipitate ventricular fibrillation in patients with Brugada syndrome. We report the case of a patient whose Brugada ECG pattern was unmasked by hyperthermia secondary to acute cholangitis. Serial ECGs showed progressive attenuation of ST segment elevation as body temperature gradually returned to normal. Structural heart disease was ruled out. Intravenous flecainide injection reproduced a less remarkable ST segment elevation. Genetic screening demonstrated a single amino acid substitution (H681P) in the SCN5A gene, thus confirming the diagnosis of Brugada syndrome. In vitro expression of this newly characterized genetic defect revealed novel biophysical abnormalities consisting of a shift in both steady-state activation and inactivation, resulting in a 60% reduction of sodium window current. Thus, SCN5A-H681P mutation induces a significant loss of transmembrane current and is clinically associated with a pathologic phenotype that is elicited by hyperthermia. Overall the observed clinical features are in agreement with previous observations and strongly suggest that fever may be an environmental modifier among Brugada syndrome patients with a detrimental (and possibly arrhythmogenic) effect on cardiac repolarization.

Original languageEnglish
Pages (from-to)407-411
Number of pages5
JournalJournal of Cardiovascular Electrophysiology
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

Keywords

  • Brugada syndrome
  • Genetics
  • Hyperthermia
  • Sodium channel

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

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