Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome.

Leomar Y. Ballester*, D. Woodrow Benson, Brenda Wong, Ian H. Law, Katherine D. Mathews, Carlos G. Vanoye, Alfred L. George

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations


Mutations in KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, have been identified in Andersen syndrome (or Andersen-Tawil syndrome), an inherited disorder characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We identified and characterized two novel KCNJ2 mutations (c.220A>G/p.T74A and c.443G>C/p.G144A) associated with Andersen syndrome. Heterologous expression of a recombinant wild type human KCNJ2 cDNA (WT-KCNJ2) in HEK-293 cells results in robust inward rectifying currents, but we did not observe measurable currents from cells expressing either mutant. Cells co-transfected with WT-KCNJ2 and either mutant exhibited substantially lower whole-cell current amplitude consistent with a dominant-negative suppression of WT-KCNJ2 by the mutant channels. Both p.T74A and p.G144A exhibit robust plasma membrane expression, but a third previously reported allele (p.C101R) exhibited impaired trafficking. Our results demonstrate functional consequences of two novel trafficking-competent KCNJ2 mutations associated with Andersen syndrome and expand our knowledge of allelic diversity in this disease. Published 2006 Wiley-Liss, Inc.

Original languageEnglish (US)
Number of pages1
JournalHuman mutation
Issue number4
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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