論文

査読有り 国際誌
2019年12月15日

Functional analysis of a double-point mutation in the KCNJ2 gene identified in a family with Andersen-Tawil syndrome.

Journal of the neurological sciences
  • Shinobu Fukumura
  • ,
  • Kosuke Yamauchi
  • ,
  • Akira Kawanabe
  • ,
  • Akiyo Yamamoto
  • ,
  • Maki Nakaza
  • ,
  • Tomoya Kubota
  • ,
  • Shinsuke Kato
  • ,
  • Ryogen Sasaki
  • ,
  • Yasushi Okamura
  • ,
  • Masanori P Takahashi

407
開始ページ
116521
終了ページ
116521
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jns.2019.116521

Andersen-Tawil syndrome (ATS) is a skeletal muscle channelopathy with autosomal dominant inheritance resulting in periodic paralysis, arrhythmia characterized by QT prolongation, and dysmorphic features. The KCNJ2 gene has been identified as the causative gene of ATS. Herein, we reported 2 cases of a 21-year-old man and his mother, with episodic paralytic attacks and/or arrhythmia, which are characteristic of ATS. Both G144A, a reported ATS mutation, and V296F, a novel mutation, were identified in the KCNJ2 gene on the same allele from the proband and his mother, but not from his father. In the present study, we investigated the functional effect of these variants on the potassium channel Kir2.1 and the significance of the double mutation. G144A, V296F, and G144A-V296F mutant channels expressed in cultured cells revealed a loss-of-function effect of these mutations on Kir2.1. The K+ currents of G144A and G144A-V296F channels were more suppressed than that of V296F channel alone, whereas was no difference between G144A and G144A-V296F. To our knowledge, a double mutation in the KCNJ2 gene has not been reported previously. While either of 2 mutations potentially causes ATS, the G144A mutation might cause the dominant effect on the patients' clinical presentation.

リンク情報
DOI
https://doi.org/10.1016/j.jns.2019.116521
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31669729
ID情報
  • DOI : 10.1016/j.jns.2019.116521
  • PubMed ID : 31669729

エクスポート
BibTeX RIS