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Autosomal recessive Andersen–Tawil syndrome with a novel mutation L94P in Kir2.1
Author(s) -
Takeda Ikuko,
Takahashi Tetsuya,
Ueno Hiroki,
Morino Hiroyuki,
Ochi Kazuhide,
Nakamura Takeshi,
Hosomi Naohisa,
Kawakami Hideshi,
Hashimoto Kouichi,
Matsumoto Masayasu
Publication year - 2013
Publication title -
neurology and clinical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2049-4173
DOI - 10.1111/ncn3.38
Subject(s) - missense mutation , green fluorescent protein , mutation , mutant , microbiology and biotechnology , wild type , medicine , genetics , biology , gene
Aim Dominant negative mutations of the inwardly rectifying K + 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. Methods We sequenced the coding region of KCJN 2 . 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 + currents using patch clamping. Results 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 ( P < 0.001). Conclusions 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.