title: 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.affiliation: Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Heron
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Smith
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Lino
authors.initials: L
authors.lastname: Nobili
authors.forename: Esther
authors.initials: E
authors.lastname: Kahana
authors.forename: Laura
authors.initials: L
authors.lastname: Licchetta
authors.forename: Karen L
authors.initials: KL
authors.lastname: Oliver
authors.forename: Aziz
authors.initials: A
authors.lastname: Mazarib
authors.forename: Zaid
authors.initials: Z
authors.lastname: Afawi
authors.forename: Amos
authors.initials: A
authors.lastname: Korczyn
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
mesh_terms: D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D059472:Exome; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human