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Different degrees of loss of function between GEFS+ and SMEI Na v 1.1 missense mutants at the same residue induced by rescuable folding defects
Author(s) -
Sugiura Yoshihiro,
Ogiwara Ikuo,
Hoshi Akihiko,
Yamakawa Kazuhiro,
Ugawa Yoshikazu
Publication year - 2012
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2012.03467.x
Subject(s) - missense mutation , nav1 , sodium channel , mutant , myoclonic epilepsy , medicine , mutation , epilepsy , chemistry , neuroscience , genetics , biology , sodium , organic chemistry , gene
Summary 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.