Double SCN5A mutation underlying asymptomatic Brugada syndrome

• Yokoi, Hisataka

• Makita, Naomasa

• Sasaki, Koji

• Takagi, Yasuhiro

• Okumura, Yasuo

• Nishino, Tetsuo

• Makiyama, Takeru

• Kitabatake, Akira

• Horie, Minoru

• Watanabe, Ichiro

• Tsutsui, Hiroyuki

Abstract

Objectives: The purpose of this study was to identify risk markers in patients with Brugada syndrome. Background: Patients with Brugada syndrome who experience syncope or aborted sudden death are at high risk for recurrent lethal arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial. Methods: We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study. Results: Twenty-nine of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient (case 1) with a family history of sudden death died suddenly during sleep. Ventricular fibrillation was induced by programmed electrical stimulation in 14 of 18 subjects (78%), but none of these 18 subjects developed spontaneous ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2). Heterologously expressed mutant Na channels exhibited a negative shift of steady-state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this individual harbors a subclinical channel dysfunction compatible with symptomatic Brugada syndrome. Conclusions: Asymptomatic individuals with a Brugada-type ECG generally have a better prognosis than their symptomatic counterparts, but a subgroup of these individuals may have a poor prognosis. Severe Na channel dysfunction as a result of SCN5A mutations may not be sufficient to cause symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown factors or modifier genes influence arrhythmogenesis.

Journal

• Heart Rhythm

  Heart Rhythm 2 (3), 285-292, 2005-03

  Heart Rhythm Society Published by Elsevier Inc.

Keywords

• Brugada syndrome
• Asymptomatic mutation carrier
• Patch clamp
• Sodium channel
• Genetics
• Slow inactivation
• SCN5A
• Ventricular fibrillation

Details

• CRID: 1050564288934822912
• NII Article ID: 120000961095
• HANDLE: 2115/16957
• ISSN: 15475271
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles