A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia

Neurogenetics. 2016 Oct;17(4):245-249. doi: 10.1007/s10048-016-0486-0. Epub 2016 Jun 8.


Episodic ataxia type 1 (EA1) is an autosomal dominant channelopathy caused by mutations in KCNA1, which encodes the voltage-gated potassium channel, Kv1.1. Eleven members of an EA family were evaluated with molecular and functional studies. A novel c.746T>G (p.Phe249Cys) missense mutation of KCNA1 segregated in the family members with episodic ataxia, myokymia, and malignant hyperthermia susceptibility. No mutations were found in the known malignant hyperthermia genes RYR1 or CACNA1S. The Phe249Cys-Kv1.1 channels did not show any currents upon functional expression, confirming a pathogenic role of the mutation. Malignant hyperthermia may be a presentation of KCNA1 mutations, which has significant implications for the clinical care of these patients and illustrates the phenotypic heterogeneity of KCNA1 mutations.

Keywords: Episodic ataxia; KCNA1; Malignant hyperthermia.

MeSH terms

  • Adolescent
  • Ataxia / complications
  • Ataxia / genetics*
  • Family
  • Female
  • Humans
  • Kv1.1 Potassium Channel / genetics*
  • Kv1.1 Potassium Channel / physiology
  • Malignant Hyperthermia / complications
  • Malignant Hyperthermia / genetics*
  • Mutation, Missense*
  • Pedigree


  • KCNA1 protein, human
  • Kv1.1 Potassium Channel

Supplementary concepts

  • Episodic Ataxia