Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia

Tomohiko Ai, Yuichiro Fujiwara, Keiko Tsuji, Hideo Otani, Shozo Nakano, Yoshihiro Kubo, Minoru Horie

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Background - Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K+ channels (Kir2.1), produce Andersen's syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results - In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2, Thr192A1a (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions - T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved amino acid residue among inward-rectifier channels. We suggest that the T192A mutation resulted in the observed electrical phenotype.

Original languageEnglish (US)
Pages (from-to)2592-2594
Number of pages3
JournalCirculation
Volume105
Issue number22
DOIs
StatePublished - Jun 5 2002
Externally publishedYes

Fingerprint

Familial Periodic Paralysis
Paralysis
Andersen Syndrome
Cardiac Arrhythmias
Mutation
Missense Mutation
Xenopus
Phosphatidylinositols
DNA Sequence Analysis
Genes
Oocytes
Binding Sites
Phenotype
Amino Acids
Polymerase Chain Reaction

Keywords

  • Arrhythmia
  • Genes
  • Ion channels
  • Paralysis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ai, T., Fujiwara, Y., Tsuji, K., Otani, H., Nakano, S., Kubo, Y., & Horie, M. (2002). Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia. Circulation, 105(22), 2592-2594. https://doi.org/10.1161/01.CIR.0000019906.35135.A3

Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia. / Ai, Tomohiko; Fujiwara, Yuichiro; Tsuji, Keiko; Otani, Hideo; Nakano, Shozo; Kubo, Yoshihiro; Horie, Minoru.

In: Circulation, Vol. 105, No. 22, 05.06.2002, p. 2592-2594.

Research output: Contribution to journalArticle

Ai, T, Fujiwara, Y, Tsuji, K, Otani, H, Nakano, S, Kubo, Y & Horie, M 2002, 'Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia', Circulation, vol. 105, no. 22, pp. 2592-2594. https://doi.org/10.1161/01.CIR.0000019906.35135.A3
Ai, Tomohiko ; Fujiwara, Yuichiro ; Tsuji, Keiko ; Otani, Hideo ; Nakano, Shozo ; Kubo, Yoshihiro ; Horie, Minoru. / Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia. In: Circulation. 2002 ; Vol. 105, No. 22. pp. 2592-2594.
@article{26b4f4affb2a48379ef599c46fb98d64,
title = "Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia",
abstract = "Background - Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K+ channels (Kir2.1), produce Andersen's syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results - In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2, Thr192A1a (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions - T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved amino acid residue among inward-rectifier channels. We suggest that the T192A mutation resulted in the observed electrical phenotype.",
keywords = "Arrhythmia, Genes, Ion channels, Paralysis",
author = "Tomohiko Ai and Yuichiro Fujiwara and Keiko Tsuji and Hideo Otani and Shozo Nakano and Yoshihiro Kubo and Minoru Horie",
year = "2002",
month = "6",
day = "5",
doi = "10.1161/01.CIR.0000019906.35135.A3",
language = "English (US)",
volume = "105",
pages = "2592--2594",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "22",

}

TY - JOUR

T1 - Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia

AU - Ai, Tomohiko

AU - Fujiwara, Yuichiro

AU - Tsuji, Keiko

AU - Otani, Hideo

AU - Nakano, Shozo

AU - Kubo, Yoshihiro

AU - Horie, Minoru

PY - 2002/6/5

Y1 - 2002/6/5

N2 - Background - Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K+ channels (Kir2.1), produce Andersen's syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results - In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2, Thr192A1a (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions - T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved amino acid residue among inward-rectifier channels. We suggest that the T192A mutation resulted in the observed electrical phenotype.

AB - Background - Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K+ channels (Kir2.1), produce Andersen's syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results - In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2, Thr192A1a (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions - T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved amino acid residue among inward-rectifier channels. We suggest that the T192A mutation resulted in the observed electrical phenotype.

KW - Arrhythmia

KW - Genes

KW - Ion channels

KW - Paralysis

UR - http://www.scopus.com/inward/record.url?scp=0037024233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037024233&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000019906.35135.A3

DO - 10.1161/01.CIR.0000019906.35135.A3

M3 - Article

C2 - 12045162

AN - SCOPUS:0037024233

VL - 105

SP - 2592

EP - 2594

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 22

ER -