A KCNQ2 E515D mutation associated with benign familial neonatal seizures and continuous spike and waves during slow-wave sleep syndrome in Taiwan
A KCNQ2 E515D mutation associated with benign familial neonatal seizures and continuous spike and waves during slow-wave sleep syndrome in Taiwan
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DOI：
10.1016/j.jfma.2016.11.009
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发表时间：
2017-09-01
影响因子：
3.2
通讯作者：
Li, Shuan-Yow
中科院分区：
文献类型：
--
作者：
Lee, Inn-Chi;Yang, Jiann-Jou;Li, Shuan-Yow
背景/目的：由KCNQ 2基因突变引起的儿童癫痫通常在出生后第1周表现为良性家族性新生儿癫痫发作（BFNS）。然而，确切的机制，表型，和基因型的KCNQ 2 mutation.Methods：我们研究了KCNQ 2基因型从75 noncrossingineous儿童癫痫患者没有一个确定的原因（年龄范围：从2天到18岁）和55个健康的成年对照无癫痫。将KCNQ 2突变变体转染到HEK 293细胞中，以研究它们诱导的功能变化。结果：四名（5%）患者具有E515 D KCNQ 2突变，基于计算机的PolyPhen算法预测其是有害的。他们的癫痫发作结果是有利的，但有三个智力残疾。2例E515 D患者在慢波睡眠（CSWS）期间出现连续棘波和波，另2例出现BFNS。我们还分析了10个具有相同KCNQ 2突变的受累家族成员：均患有癫痫（8例BFNS，2例CSWS）。功能分析表明，E515 D电流的记录有显着差异，（p < 0.05），这表明与野生型或N780 T相比，KCNQ 2 E515 D变体通道对电压的敏感性较低，需要更强的去极化才能达到开放概率结论：KCNQ 2基因突变可导致儿童多种表型：BFNS和CSWS。我们假设KCNQ 2 E515 D突变的患者易患癫痫发作。版权所有（C）2016，台湾医学会.出版社：Elsevier Taiwan LLC
Background/Purpose: Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests as benign familial neonatal seizures (BFNS) during the 1st week of life. However, the exact mechanism, phenotype, and genotype of the KCNQ2 mutation are unclear.Methods: We studied the KCNQ2 genotype from 75 nonconsanguineous patients with childhood epilepsy without an identified cause (age range: from 2 days to 18 years) and from 55 healthy adult controls without epilepsy. KCNQ2 mutation variants were transfected into HEK293 cells to investigate what functional changes they induced.Results: Four (5%) of the patients had the E515D KCNQ2 mutation, which the computer-based PolyPhen algorithm predicted to be deleterious. Their seizure outcomes were favorable, but three had an intellectual disability. Two patients with E515D presented with continuous spikes and waves during slow-wave sleep (CSWS), and the other two presented with BFNS. We also analyzed 10 affected family members with the same KCNQ2 mutation: all had epilepsy (8 had BFNS and 2 had CSWS). A functional analysis showed that the recordings of the E515D currents were significantly different (p < 0.05), which suggested that channels with KCNQ2 E515D variants are less sensitive to voltage and require stronger depolarization to reach opening probabilities than those with the wild type or N780T (a benign polymorphism).Conclusion: KCNQ2 mutations can cause various phenotypes in children: they lead to BFNS and CSWS. We hypothesize that patients with the KCNQ2 E515D mutation are susceptible to seizures. Copyright (C) 2016, Formosan Medical Association. Published by Elsevier Taiwan LLC.