Abstract | OBJECTIVE: METHODS: The proband exhibited episodic flaccid weakness and a characteristic TU-wave pattern, both suggestive of Andersen-Tawil syndrome, but did not harbor KCNJ2 mutations. We performed exome capture resequencing by restricting the analysis to genes that encode ion channels/associated proteins. The expression of gene products in heart and skeletal muscle tissues was examined by immunoblotting. The functional consequences of the mutation were investigated using a heterologous expression system in Xenopus oocytes, focusing on the interaction with the Kir2.1 subunit. RESULTS: We identified a mutation in the KCNJ5 gene, which encodes the G-protein-activated inwardly rectifying potassium channel 4 (Kir3.4). Immunoblotting demonstrated significant expression of the Kir3.4 protein in human heart and skeletal muscles. The coexpression of Kir2.1 and mutant Kir3.4 in Xenopus oocytes reduced the inwardly rectifying current significantly compared with that observed in the presence of wild-type Kir3.4. CONCLUSIONS:
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Authors | Yosuke Kokunai, Tomohiko Nakata, Mitsuru Furuta, Souhei Sakata, Hiromi Kimura, Takeshi Aiba, Masao Yoshinaga, Yusuke Osaki, Masayuki Nakamori, Hideki Itoh, Takako Sato, Tomoya Kubota, Kazushige Kadota, Katsuro Shindo, Hideki Mochizuki, Wataru Shimizu, Minoru Horie, Yasushi Okamura, Kinji Ohno, Masanori P Takahashi |
Journal | Neurology
(Neurology)
Vol. 82
Issue 12
Pg. 1058-64
(Mar 25 2014)
ISSN: 1526-632X [Electronic] United States |
PMID | 24574546
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- G Protein-Coupled Inwardly-Rectifying Potassium Channels
- KCNJ2 protein, human
- Potassium Channels, Inwardly Rectifying
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Topics |
- Adult
- Andersen Syndrome
(genetics, physiopathology)
- Animals
- Cohort Studies
- Exome
(genetics)
- G Protein-Coupled Inwardly-Rectifying Potassium Channels
(genetics)
- Humans
- Japan
- Male
- Muscle, Skeletal
(metabolism)
- Mutation
- Myocardium
(metabolism)
- Oocytes
(metabolism)
- Pedigree
- Potassium Channels, Inwardly Rectifying
(antagonists & inhibitors, genetics)
- Xenopus
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