Different degrees of loss of function between GEFS+ and SMEI Nav1.1 missense mutants at the same residue induced by rescuable folding defects
Different degrees of loss of function between GEFS+ and SMEI Nav1.1 missense mutants at the same residue induced by rescuable folding defects
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DOI：
10.1111/j.1528-1167.2012.03467.x
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发表时间：
2012-06
期刊：
影响因子：
5.6
通讯作者：
Y. Sugiura;I. Ogiwara;A. Hoshi;K. Yamakawa;Y. Ugawa
中科院分区：
文献类型：
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作者：
Y. Sugiura;I. Ogiwara;A. Hoshi;K. Yamakawa;Y. Ugawa
全身性癫痫伴热性发作+ (GEFS+)和婴儿期严重肌阵挛性癫痫（SMEI）的临床严重程度和预后不同，尽管这两种疾病都是由Nav1.1钠通道突变引起的。我们比较了两个在相同残基位置具有不同氨基酸取代的突变体：GEFS+ (A1685V)和SMEI （A1685D）的电生理特性。这两种突变体在单独表达时都表现出完全丧失功能。然而，A1685V的功能可以被β1亚基部分挽救，与折叠缺陷一致，而A1685D的功能则没有被挽救。这些电生理差异与GEFS+和SMEI在临床严重程度上的差异是一致的。
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 Nav1.1 sodium channel are responsible for both disorders. We compared the electrophysiologic properties of two mutant Nav1.1 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 β1 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.