title: Nav1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents.
abstract: Severe myoclonic epilepsy in infancy (SMEI) is characterized by intractable febrile and afebrile seizures, severe mental decline, and onset during the first year of life. Nonsense, frameshift, and missense mutations of SCN1A gene encoding the voltage-gated Na(+) channel alpha-subunit type I (Na(v)1.1) have been identified in patients with SMEI. Here, we performed whole-cell patch-clamp analyses on HEK293 cells expressing human Na(v)1.1 channels bearing SMEI nonsense and missense mutations. The mutant channels showed remarkably attenuated or barely detectable inward sodium currents. Our findings indicate that SMEI mutations lead to loss-of-function and may contribute to the development of SMEI phenotypes.
authors.affiliation: Laboratory for Neurogenetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tsurubuchi
authors.forename: Tateki
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Emi
authors.initials: E
authors.lastname: Mazaki-Miyazaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nagata
authors.forename: Mauricio
authors.initials: M
authors.lastname: Montal
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
mesh_terms: D002460:Cell Line; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D006801:Humans; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels