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Double SCN5A mutation underlying asymptomatic Brugada syndrome

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Title: Double SCN5A mutation underlying asymptomatic Brugada syndrome
Authors: Yokoi, Hisataka Browse this author
Makita, Naomasa Browse this author
Sasaki, Koji Browse this author
Takagi, Yasuhiro Browse this author
Okumura, Yasuo Browse this author
Nishino, Tetsuo Browse this author
Makiyama, Takeru Browse this author
Kitabatake, Akira Browse this author
Horie, Minoru Browse this author
Watanabe, Ichiro Browse this author
Tsutsui, Hiroyuki Browse this author →KAKEN DB
Keywords: Brugada syndrome
Asymptomatic mutation carrier
Patch clamp
Sodium channel
Genetics
Slow inactivation
SCN5A
Ventricular fibrillation
Issue Date: Mar-2005
Publisher: Heart Rhythm Society Published by Elsevier Inc.
Journal Title: Heart Rhythm
Volume: 2
Issue: 3
Start Page: 285
End Page: 292
Publisher DOI: 10.1016/j.hrthm.2004.11.022
PMID: 15851320
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.
Relation: http://www.sciencedirect.com/science/journal/15475271
Type: article (author version)
URI: http://hdl.handle.net/2115/16957
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 筒井 裕之

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