title: A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.
abstract: We performed analysis of KCNT1 in two unrelated patients with malignant migrating partial seizures in infancy. Both patients had intractable focal seizures since two months of age. Their seizures were characterized by a shift of epileptic focus during a single seizure and were resistant to most antiepileptic drugs but responded to vagus nerve stimulation in one and clorazepate in the other. Bidirectional sequencing for KCNT1 was analyzed by standard Sanger sequencing method. A de novo c.862G>A (p.Gly288Ser) missense mutation was identified at the pore region of KCNT1 channel in both patients, whereas all KCNT1 mutations in the previous reports were identified mostly in the intracellular C-terminal region. Computational analysis suggested possible changes in the molecular structure and the ion channel property induced by the Gly288Ser mutation. Because the G-to-A transition was located at CG dinucleotide sequences as previously reported for KCNT1 mutations, the recurrent occurrence of de novo KCNT1 mutations indicated the hot spots of these locations.
authors.affiliation: Department of Pediatrics, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Electronic address: ishii@fukuoka-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.forename: Mutsuki
authors.initials: M
authors.lastname: Shioda
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kidokoro
authors.forename: Masako
authors.initials: M
authors.lastname: Sakauchi
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D017668:Age of Onset; D002648:Child; D004828:Epilepsies, Partial / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008954:Models, Biological; D020125:Mutation, Missense / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D000081033:Potassium Channels, Sodium-Activated; D011596:Psychomotor Disorders / Q000150:complications / Q000235:genetics
chemical_list: C585122:KCNT1 protein, human; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated
keywords: ADNFLE; CLZ; Clorazepate; Hot spot; KCNT1; MMPSI; MOE; Malignant migrating partial seizures in infancy; Molecular operating environment; Vagus nerve stimulation; autosomal dominant nocturnal frontal lobe epilepsy; clorazepate; malignant migrating partial seizures in infancy; molecular operating environment