KCNE5 Variants Are Novel Modulators of Brugada Syndrome and Idiopathic Ventricular Fibrillation
スポンサーリンク
概要
- 論文の詳細を見る
Brugada syndrome (BrS) and idiopathic ventricular fibrillation (IVF) have a higher incidence among males. Among genes coding ion channels, KCNE5 is located in the X chromosome, encodes an auxiliary subunit for K channels and modifies the transient outward current (I<SUB>to</SUB>). In 205 Japanese patients with BrS or IVF, who were negative for SCN5A mutation, we conducted a genetic screen for KCNE5 and identified two novel KCNE5 variants, Y81H in 1 male and 2 female, and D92E-E93X in one male from 4 unrelated families. All probands received ICD implantation. Functional consequences of the KCNE5 variants were determined through biophysical assay using co-transfection with KCND3 or KCNQ1. In the experiments with KCND3, I<SUB>to</SUB> was significantly increased for both of the KCNE5 variants compared to WT. In contrast, there were no significant changes in KCNQ1+KCNE5 WT and the two variants. With the simulation model, both variants demonstrated "notch and dome" or "loss of dome" patterns. In conclusion, novel KCNE5 variants increased I<SUB>to</SUB> and appeared to cause ventricular fibrillation. Screening for KCNE5 is relevant for BrS or IVF.
著者
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Hattori Tetsuhisa
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
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Shizuta Satoshi
Department Of Cardiology Juntendo Shizuoka Hospital
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Matsuura hiroshi
Department of Physiology, Shiga University of Medical Science
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Makiyama Takeru
Department Of Cardiology Hyogo Prefectural Amagasaki Hospital
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Matsuura Hiroshi
Department Of Applied Biological Chemistry Graduate School Of Agricultural And Life Sciences The Uni
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Hattori Tetsuhisa
Department Of Cardiovascular Medicine Kyoto University
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Horie Minoru
Department Of Cardiac Physiology National Cardiovascular Center Research Institute
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Ding Wei-guang
Department Of Physiology Shiga University Of Medical Science
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Naiki Nobu
Department Of Cardiology Nagahama City Hospital
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Itoh Hideki
Department Of Anesthesiology And Critical Care Medicine Yokohama City University Graduate School Of
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Miyamoto Akashi
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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Doi Takahiro
Department Of Cardiology Kokura Memorial Hospital
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Ohno Seiko
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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Itoh Hideki
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
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Shizuta Satoshi
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
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P. Zankov
Department of Physiology, Shiga University of Medical Science
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Hattori Tetsuhisa
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
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