Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher’s test, p = 2.02 × 10⁻⁶, adjusted α = 4.52 × 10⁻⁶). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.

基因亚区编码的蛋白质结构域是蛋白质结构和功能的基本单位。DMD基因是人类最大的编码基因，其表型与特发性全身性癫痫相关。我们假设变异聚集在特发性全身性癫痫基因的亚区域，并研究了DMD基因与特发性全身性癫痫之间的关系。对 106 名特发性全身性癫痫患者进行了全外显子组测序。DMD变体通过变体类型、等位基因频率、计算机预测、群体中的半合子或纯合状态、遗传模式和域位置进行过滤。subRVIS 软件选择位于子区域的变体。变异的致病性按照美国医学遗传学和基因组学标准进行评估。回顾了与癫痫相关的变异蛋白结构域功能研究的文章。在DMD基因的子区域中，在两例无关的青少年失神性癫痫或青少年肌阵挛性癫痫病例中发现了两种变异。两种变异体的致病性意义均不确定。与人群相比，特发性全身性癫痫先证者中两种变异的等位基因频率均达到统计学显着性（Fisher 检验，p  = 2.02 × 10 ^-6，调整后的α  = 4.52 × 10 ^-6）。这些变体聚集在肌营养不良蛋白的血影蛋白结构域中，该结构域与糖蛋白复合物结合并间接影响导致癫痫发生的离子通道。基因亚区域分析表明DMD基因与特发性全身性癫痫之间的关联较弱。基因亚区的功能分析有助于推断特发性全身性癫痫的发病机制。