A novel KCNA1 mutation causing episodic ataxia type I

Saskia Lassche, Sergio Lainez, Bastiaan R. Bloem, Bart P.C. van de Warrenburg, Jeannette Hofmeijer, Henny H. Lemmink, Joost G.J. Hoenderop, René J.M. Bindels, Gea Drost*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

We describe the clinical phenotype of a novel de novo KNCA1 mutation, and functional characterization of the effects of the mutation on Kv1.1 channel function. HEK293 cells were transfected transiently with either wild-type or mutant channels. Representative currents were evoked after application of a series of square voltage steps from -80 mV to +50 mV in 200-ms intervals from Vh = -80 mV. Extracellular K+ was added to evoke tail currents. Equal amounts of wild-type and Kv1.1I262M mutant DNA were transfected transiently in HEK293 cells to evaluate the influence of the mutation. We found that Kv1.1I262M leads to a defective voltage-gated potassium channel. Coexpression studies revealed a dominant-negative effect. We describe the phenotype of a novel KCNA1 mutation causing episodic ataxia. Patch-clamp studies confirm the pathogenicity of the mutation in vitro and suggest that it is dominant with respect to wild-type.

Original languageEnglish
Pages (from-to)289-291
Number of pages3
JournalMuscle and Nerve
Volume50
Issue number2
DOIs
Publication statusPublished - 1 Aug 2014

Keywords

  • Channelopathy
  • Episodic ataxia type 1
  • Ion channels
  • KCNA1
  • Potassium channel

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    Lassche, S., Lainez, S., Bloem, B. R., van de Warrenburg, B. P. C., Hofmeijer, J., Lemmink, H. H., ... Drost, G. (2014). A novel KCNA1 mutation causing episodic ataxia type I. Muscle and Nerve, 50(2), 289-291. https://doi.org/10.1002/mus.24242