title: Novel brugada SCN5A mutation leading to ST segment elevation in the inferior or the right precordial leads.
abstract: Mutations in the SCN5A gene can lead to the Brugada syndrome, a genetically inherited form of idiopathic ventricular fibrillation that has a characteristic ECG phenotype usually restricted to precordial leads V1-V3. We identified a novel G752R SCN5A missense mutation leading to various degrees of the Brugada ECG phenotype in members of a French family. In the proband, the G752R mutation produced ST segment elevation and prominent J wave in leads II, III, and aVF. In four other relatives, ST segment elevation in the right precordial but not in the inferior leads was observed either spontaneously or under flecainide challenge. Recombinant G752R mutant exhibited a markedly reduced Na+ current amplitude and a voltage shift in both activation and inactivation curves. The mutant was found in all affected but not in nonaffected family members. One additional gene-carrier had an almost normal ECG (silent gene-carrier). We provide genetic demonstration that Brugada ECG anomalies related to a unique SCN5A mutation can be observed either in the inferior or the right precordial leads.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U533, Faculté de Médecine, the Cardiology Department, Hôpital G&R Laennec, Nantes, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Potet
authors.forename: Philippe
authors.initials: P
authors.lastname: Mabo
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Coq
authors.forename: Vincent
authors.initials: V
authors.lastname: Probst
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Schott
authors.forename: Fabrice
authors.initials: F
authors.lastname: Airaud
authors.forename: Gilles
authors.initials: G
authors.lastname: Guihard
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Daubert
authors.forename: Denis
authors.initials: D
authors.lastname: Escande
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Marec
mesh_terms: D000328:Adult; D002037:Bundle-Branch Block / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels