KCNE5 Variants Are Novel Modulators of Brugada Syndrome and Idiopathic Ventricular Fibrillation

Seiko Ohno; Dimitar P. Zankov; Wei-Guang Ding; Hideki Itoh; Takeru Makiyama; Takahiro Doi; Satoshi Shizuta; Tetsuhisa Hattori; Akashi Miyamoto; Nobu Naiki; Hiroshi Matsuura; Minoru Horie

doi:10.4020/jhrs.27.YIAB_5

Chairs: Hung-Fat Tse (Hong Kong), Haruaki Nakaya (Japan)
Juries: Itsuo Kodama (Japan), Choong-Hwan Kwak (Korea), Katsushige Ono (Japan), Robert S. Kass (USA), Michiel J. Janse (Netherlands)

KCNE5 Variants Are Novel Modulators of Brugada Syndrome and Idiopathic Ventricular Fibrillation

Seiko Ohno, Dimitar P. Zankov, Wei-Guang Ding, Hideki Itoh, Takeru Makiyama, Takahiro Doi, Satoshi Shizuta, Tetsuhisa Hattori, Akashi Miyamoto, Nobu Naiki, Hiroshi Matsuura, Minoru Horie

Author information

Seiko Ohno
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
Dimitar P. Zankov
Department of Physiology, Shiga University of Medical Science
Wei-Guang Ding
Department of Physiology, Shiga University of Medical Science
Hideki Itoh
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
Takeru Makiyama
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Takahiro Doi
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Satoshi Shizuta
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Tetsuhisa Hattori
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Akashi Miyamoto
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
Nobu Naiki
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
Hiroshi Matsuura
Department of Physiology, Shiga University of Medical Science
Minoru Horie
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science

Keywords: KCNE5, IVF, Brugada syndrome

JOURNAL FREE ACCESS

2011 Volume 27 Issue Supplement Pages YIAB_5

DOI https://doi.org/10.4020/jhrs.27.YIAB_5

Details

Abstract

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_to). 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_to 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_to and appeared to cause ventricular fibrillation. Screening for KCNE5 is relevant for BrS or IVF.

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