Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy

Nat Genet. 2012 Nov;44(11):1188-90. doi: 10.1038/ng.2440. Epub 2012 Oct 21.

Abstract

We performed genomic mapping of a family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and intellectual and psychiatric problems, identifying a disease-associated region on chromosome 9q34.3. Whole-exome sequencing identified a mutation in KCNT1, encoding a sodium-gated potassium channel subunit. KCNT1 mutations were identified in two additional families and a sporadic case with severe ADNFLE and psychiatric features. These findings implicate the sodium-gated potassium channel complex in ADNFLE and, more broadly, in the pathogenesis of focal epilepsies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epilepsy, Frontal Lobe / genetics*
  • Exome
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels / genetics*
  • Mutation, Missense / genetics*
  • Pedigree
  • Sequence Analysis, DNA

Substances

  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNN4 protein, human