Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis
Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis
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DOI：
10.1212/01.wnl.0000342387.65477.46
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发表时间：
2009-05-05
期刊：
影响因子：
9.9
通讯作者：
Hanna, M. G.
中科院分区：
文献类型：
--
作者：
Matthews, E.;Labrum, R.;Hanna, M. G.
背景：低血钾性周期性麻痹患者存在CACNA1S和SCN4A基因的多个错义突变。这些突变会影响通道的S4电压传感器中的精氨酸残基。方法：我们对83例低钾性周期性麻痹患者进行了CACNA1S和SCN4A基因S4区的直接DNA自动测序。结果：在病例中发现CACNA1S基因突变。在其余19例中，有10例发现了SCN4A或其他CACNA1S S4片段的突变，其中包括3个新的突变，以及通道结构域I(SCN4A)和通道结构域III(CACNA1S)的首次突变。结论：所有突变均影响精氨酸残基，符合低钾性周期性麻痹的门控孔阳离子泄漏假说。S4节段的精氨酸突变是90%的低钾性周期性麻痹病例的基础。神经病学(R)2009；72：1544-1547
Background: Several missense mutations of CACNA1S and SCN4A genes occur in hypokalemic periodic paralysis. These mutations affect arginine residues in the S4 voltage sensors of the channel. Approximately 20% of cases remain genetically undefined.Methods: We undertook direct automated DNA sequencing of the S4 regions of CACNA1S and SCN4A in 83 cases of hypokalemic periodic paralysis. Results: We identified reported CACNA1S mutations in 64 cases. In the remaining 19 cases, mutations in SCN4A or other CACNA1S S4 segments were found in 10, including three novel changes and the first mutations in channel domains I (SCN4A) and III (CACNA1S).Conclusions: All mutations affected arginine residues, consistent with the gating pore cation leak hypothesis of hypokalemic periodic paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic paralysis cases. Neurology (R) 2009;72:1544-1547