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

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.

• Authors: Sarah E Heron, Katherine R Smith, Melanie Bahlo, Lino Nobili, Esther Kahana, Laura Licchetta, Karen L Oliver, Aziz Mazarib, Zaid Afawi, Amos Korczyn, Giuseppe Plazzi, Steven Petrou, Samuel F Berkovic, Ingrid E Scheffer, Leanne M Dibbens
• Journal: Nature genetics (Nat Genet) Vol. 44 Issue 11 Pg. 1188-90 (Nov 2012) ISSN: 1546-1718 [Electronic] United States
• PMID: 23086396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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