Autosomal recessive Andersen–Tawil syndrome with a novel mutation L94P in Kir2.1. Issue 4 (26th August 2013)

• Record Type: Journal Article
• Authors: Takeda, Ikuko; Takahashi, Tetsuya; Ueno, Hiroki; Morino, Hiroyuki; Ochi, Kazuhide; Nakamura, Takeshi; Hosomi, Naohisa; Kawakami, Hideshi; Hashimoto, Kouichi; Matsumoto, Masayasu
• Is Part Of: Neurology and clinical neuroscience. Volume 1:Issue 4(2013:Jul.)
• Page Start: 131
• Page End: 137
• Publication Date: 2013-08-26
• Subjects: Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8
• DOI: 10.1111/ncn3.38
• Languages: English
• ISSNs: 2049-4173

Abstract

<abstract abstract-type="main" id="ncn338-abs-0001"> <title>Abstract</title> <sec id="ncn338-sec-0001" sec-type="section"> <title>Aim</title> <p>Dominant negative mutations of the inwardly rectifying K<sup>+</sup> channel, Kir2.1, cause Andersen–Tawil syndrome (ATS), an autosomal dominant disorder. Here, we identified a novel Kir2.1 mutation causing autosomal recessive ATS, and explored the underlying mechanism.</p> </sec> <sec id="ncn338-sec-0002" sec-type="section"> <title>Methods</title> <p>We sequenced the coding region of <italic>KCJN2</italic>. We assessed protein subcellular localization by transfecting cells with Kir2.1‐enhanced green fluorescent protein fusions and observing them by confocal microscopy. We measured K<sup>+</sup> currents using patch clamping.</p> </sec> <sec id="ncn338-sec-0003" sec-type="section"> <title>Results</title> <p>We identified the novel Kir2.1 missense mutation L94P in a patient with ATS. L94P‐enhanced green fluorescent protein (EGFP) was barely detected at the plasma membrane, in contrast to wild‐type (WT)‐EGFP and L94P‐EGFP + WT. The excitability of L94P‐expressing cells was significantly lower than that of WT‐expressing cells and L94P + WT‐expressing cells (<italic>P </italic><<italic> </italic>0.001).</p> </sec> <sec id="ncn338-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Most L94P mutant Kir2.1 fails to reach the plasma membrane, but heterotetrameric channels comprising L94P + WT can traffic normally to the plasma membrane and generate currents. The L94P mutation is transmitted as an autosomal recessive trait.</p> </sec> </abstract>