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Double SCN5A mutation underlying asymptomatic Brugada syndrome
| 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)
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Submitter: 筒井 裕之
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