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Double SCN5A mutation underlying asymptomatic Brugada syndrome.

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_name

Heart Rhythm

journal_title

Heart rhythm

authors

Yokoi H,Makita N,Sasaki K,Takagi Y,Okumura Y,Nishino T,Makiyama T,Kitabatake A,Horie M,Watanabe I,Tsutsui H

doi

10.1016/j.hrthm.2004.11.022

keywords:

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

285-92

issue

3

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(04)00804-5

journal_volume

2

pub_type

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