Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia.

Authors: Ai, T  Fujiwara, Y  Tsuji, K  Otani, H  Nakano, S  Kubo, Y  Horie, M 
Citation: Ai T, etal., Circulation. 2002 Jun 4;105(22):2592-4.
Pubmed: (View Article at PubMed) PMID:12045162

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, Thr192Ala (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.


Disease Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 1580802
Created: 2006-08-25
Species: All species
Last Modified: 2006-08-25
Status: ACTIVE