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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuji
authors.forename: Hideo
authors.initials: H
authors.lastname: Otani
authors.forename: Shozo
authors.initials: S
authors.lastname: Nakano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kubo
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D019943:Amino Acid Substitution; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D010245:Paralyses, Familial Periodic / Q000175:diagnosis / Q000235:genetics*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics*; D013577:Syndrome; D014162:Transfection; D018754:Ventricular Dysfunction / Q000175:diagnosis / Q000235:genetics*; D014981:Xenopus
chemical_list: D024661:Potassium Channels, Inwardly Rectifying