E-resources
Peer reviewed
Open access
-
Ohno, Seiko; Zankov, Dimitar P; Ding, Wei-Guang; Itoh, Hideki; Makiyama, Takeru; Doi, Takahiro; Shizuta, Satoshi; Hattori, Tetsuhisa; Miyamoto, Akashi; Naiki, Nobu; Hancox, Jules C; Matsuura, Hiroshi; Horie, Minoru
Circulation. Arrhythmia and electrophysiology 4, Issue: 3Journal Article
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.
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.