Many questions remain regarding the genetics of idiopathic generalized epilepsy (IGE), a subset of genetic generalized epilepsy (GGE). We aimed to identify the candidate coding variants of epilepsy panel genes in a cohort of affected individuals, using variant frequency information from a control cohort of the same region. We performed whole-exome sequencing analysis of 121 individuals and 10 affected relatives, focusing on variants of 950 candidate genes associated with epilepsy according to the Genes4Epilepsy curated panel. We identified 168 candidate variants (CVs) in 137 of 950 candidate genes in 88 of 121 affected individuals with IGE, of which 61 were novel variants. Notably, we identified five CVs in known GGE-associated genes (CHD2, GABRA1, RORB, SCN1A, and SCN1B) in five individuals and CVs shared by affected individuals in each of four family cases for other epilepsy candidate genes. The results of this study demonstrate that IGE is a disease with high heterogeneity and provide IGE-associated CVs whose pathogenicity should be proven by future studies, including advanced functional analysis. The low detection rate of CVs in the GGE-associated genes (4.1%) in this study suggests the current incompleteness of the Genes4Epilepsy panel for the diagnosis of IGE in clinical practice.

关于特发性全身性癫痫（IGE）（遗传性全身性癫痫（GGE）的一个子集）的遗传学仍存在许多问题。我们的目的是利用来自同一地区对照队列的变异频率信息，识别一组受影响个体中癫痫组基因的候选编码变异。我们对 121 名个体和 10 名患病亲属进行了全外显子组测序分析，根据 Genes4Epilepsy 策划的小组，重点关注与癫痫相关的 950 个候选基因的变异。我们在 121 名 IGE 患者中的 88 名患者的 950 个候选基因中的 137 个中鉴定出了 168 个候选变异 (CV)，其中 61 个是新变异。值得注意的是，我们在 5 个个体中识别出已知 GGE 相关基因（CHD2、GABRA1、RORB、SCN1A和SCN1B）中的 5 个 CV，以及在其他癫痫候选基因的 4 个家庭病例中每个病例中受影响个体共享的 CV。这项研究的结果表明，IGE 是一种具有高度异质性的疾病，并提供了 IGE 相关的 CV，其致病性应通过未来的研究（包括高级功能分析）来证明。本研究中 GGE 相关基因 CV 的低检出率 (4.1%) 表明，目前临床实践中用于诊断 IGE 的 Genes4Epilepsy 组合并不完整。