Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1

Kir2.1に新規ミスセンス変異（L94P）を認める常染色体劣性遺伝形式のAndersen-Tawil症候群

Takeda Ikuko

Aim: Dominant negative mutations of the inwardly rectifying K+ channel Kir2.1 cause Andersen-Tawil syndrome, 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 KCJN2. 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. L94P-EGFP was barely detected at the plasma membrane, in contrast to WT-EGFP and L94PEGFP+WT. The excitability of L94P-expressing cells was decreased compared with 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.

Andersen-Tawil syndrome

KCNJ2

Kir2.1

autosomal recessive

patch clamp

Medical sciences [ 490 ]

eng

Copyright(c) by Author

[Created] 2014-11-21

Ikuko Takeda, Tetsuya Takahashi, Hiroki Ueno, Hiroyuki Morino, Kazuhide Ochi, Takeshi Nakamura, Naohisa Hosomi, Hideshi Kawakami, Kouichi Hashimoto and Masayasu Matsumoto; Autosomal recessive Andersen-Tawil syndrome with a novel mutation L94P in Kir2.1; Neurology and Clinical Neuroscience, Volume 1, Issue 4, pages 131-137, July 2013 (doi: 10.1111/ncn3.38) references

[DOI] http://dx.doi.org/10.1111/ncn3.38 references

広島大学