Referenced in: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.3 , Kv7.1 , Nav1.5

Title: KCNE5 (KCNE1L) Variants Are Novel Modulator of Brugada Syndrome and Idiopathic Ventricular Fibrillation.

Authors: Seiko Ohno, Dimitar P Zankov, Wei-Guang Ding, Hideki Itoh, Takeru Makiyama, Takahiro Doi, Satoshi Shizuta, Tetsuhisa Hattori, Akashi Miyamoto, Nobu Naiki, Jules C Hancox, Hiroshi Matsuura, Minorou Horie

Journal, date & volume: , 2011 Apr 14 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21493962

Abstract
Brugada syndrome (BrS) has a significantly higher incidence among the male sex. Among genes coding ion channels and their modulatory proteins, KCNE5 (KCNE1L) is located in the X chromosome and encodes an auxiliary β-subunit for K channels. KCNE5 has been shown to modify the transient outward current (I(to)), which plays a key role in determining the repolarization process in the myocardium. This study investigated whether KCNE5 mutations could be responsible for BrS and other idiopathic ventricular fibrillation (IVF).In 205 Japanese patients with BrS or IVF who tested negative for SCN5A mutation, we conducted a genetic screen for KCNE5 variants. We identified 2 novel KCNE5 variants: p.Y81H in 3 probands and p.[D92E;E93X] in 1 proband from 4 unrelated families. Y81H was identified in 1 man and 2 women; D92E;E93X was found in a 59-year-old man. All probands received implantable cardioverter-defibrillators. Functional consequences of the KCNE5 variants were determined through biophysical assay using cotransfection with KCND3 or KCNQ1. In the experiments with KCND3, which encodes Kv4.3, I(to) was significantly increased for both KCNE5 variants compared to wild type. In contrast, there were no significant changes in current properties reconstructed by KCNQ1+ wild type KCNE5 and the 2 variants. With the simulation model, both variants demonstrated notch-and-dome or loss-of-dome patterns.KCNE5 modulates I(to), and its novel variants appeared to cause IVF, especially BrS, in male patients through gain-of-function effects on I(to). Screening for KCNE5 variants is relevant for BrS or IVF.