Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Genetics Laboratory and Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
J Formos Med Assoc. 2017 Sep;116(9):711-719. doi: 10.1016/j.jfma.2016.11.009. Epub 2016 Dec 27.
BACKGROUND/PURPOSE: Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests as benign familial neonatal seizures (BFNS) during the 1 week of life. However, the exact mechanism, phenotype, and genotype of the KCNQ2 mutation are unclear.
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.
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).
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.
背景/目的：由 KCNQ2 基因突变引起的小儿癫痫通常在生命的第 1 周表现为良性家族性新生儿癫痫（BFNS）。然而，确切的机制、表型和 KCNQ2 突变的基因型尚不清楚。
我们研究了 75 名无明确病因的儿童期癫痫（年龄范围：2 天至 18 岁）非近亲患者和 55 名无癫痫的健康成年对照者的 KCNQ2 基因型。将 KCNQ2 突变变体转染到 HEK293 细胞中，以研究它们引起的功能变化。
4 名（5%）患者携带 KCNQ2 E515D 突变，计算机预测该突变是有害的。他们的癫痫发作结局良好，但其中 3 人有智力残疾。2 名 E515D 患者表现为慢波睡眠期间连续棘波和尖波（CSWS），另 2 名患者表现为 BFNS。我们还分析了 10 名携带相同 KCNQ2 突变的受影响家族成员：所有人均患有癫痫（8 人患有 BFNS，2 人患有 CSWS）。功能分析显示，E515D 电流的记录明显不同（p<0.05），这表明 KCNQ2 E515D 变体的通道对电压的敏感性较低，需要更强的去极化才能达到比野生型或 N780T（良性多态性）更高的开放概率。
KCNQ2 突变可导致儿童出现多种表型：导致 BFNS 和 CSWS。我们假设 KCNQ2 E515D 突变的患者易发生癫痫发作。
