Loss-of-function KCNH2 mutation in a family with long QT syndrome, epilepsy, and sudden death

Epilepsia. 2013 Aug;54(8):e112-6. doi: 10.1111/epi.12259.


There has been increased interest in a possible association between epilepsy channelopathies and cardiac arrhythmias, such as long QT syndrome (LQTS). We report a kindred that features LQTS, idiopathic epilepsy, and increased risk of sudden death. Genetic study showed a previously unreported heterozygous point mutation (c.246T>C) in the KCNH2 gene. Functional studies showed that the mutation induces severe loss of function. This observation provides further evidence for a possible link between idiopathic epilepsy and LQTS.

Keywords: Channelopathy; Epilepsy; KCNH2; Long QT syndrome; Sudden death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biophysical Phenomena / genetics
  • Cell Line, Transformed
  • DNA Mutational Analysis
  • Death, Sudden*
  • ERG1 Potassium Channel
  • Electric Stimulation
  • Electrocardiography
  • Epilepsy / complications
  • Epilepsy / genetics*
  • Ether-A-Go-Go Potassium Channels / genetics*
  • Family Health*
  • Female
  • Humans
  • Long QT Syndrome / complications
  • Long QT Syndrome / genetics*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Patch-Clamp Techniques
  • Point Mutation / genetics
  • Transfection
  • Twins, Dizygotic / genetics


  • Bacterial Proteins
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria