title: Different degrees of loss of function between GEFS+ and SMEI Nav 1.1 missense mutants at the same residue induced by rescuable folding defects.
abstract: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) differ in their clinical severity and prognosis even though mutations of the Na(v) 1.1 sodium channel are responsible for both disorders. We compared the electrophysiologic properties of two mutant Na(v) 1.1 channels characterized by distinct amino acid substitutions at the same residue position: GEFS+ (A1685V) and SMEI (A1685D). Both the mutants showed complete loss of function when expressed alone. However, the function of A1685V can be partly rescued by the β(1)  subunit, consistently with a folding defect, whereas that of A1685D was not rescued. These electrophysiologic differences are consistent with the divergence in clinical severity between GEFS+ and SMEI.
authors.affiliation: Department of Neurology, Fukushima Medical University, Fukushima, Japan. y-sugiura@umin.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ogiwara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hoshi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ugawa
mesh_terms: D001120:Arginine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D001703:Biophysics; D002461:Cell Line, Transformed; D004558:Electric Stimulation; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D006801:Humans; D008564:Membrane Potentials / Q000235:genetics*; D020125:Mutation, Missense / Q000502:physiology*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D003294:Seizures, Febrile / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods; D014633:Valine / Q000235:genetics
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D001224:Aspartic Acid; D001120:Arginine; D014633:Valine