摘要目的:探讨经二代测序确诊的 GRIN2A基因变异所致癫痫失语疾病谱患儿的临床表型特征及基因变异特点。 方法:回顾性分析2019年2月至2022 年11 月郑州大学附属儿童医院神经内科确诊的5例以癫痫起病的癫痫失语疾病谱患儿的临床资料，采用二代测序方法对先证者进行全外显子基因组测序，证实5例均为 GRIN2A基因变异患儿，并通过一代Sanger测序对家系成员进行验证以确认变异来源，对 GRIN2A基因变异特点进行分析。 结果:5例确诊为 GRIN2A基因变异所致癫痫失语疾病谱的患儿中，男女比例为4∶1，起病年龄范围为1.5~4.4岁。临床表型均有癫痫发作，4例有语言及智能发育落后；3例共患有注意力缺陷多动障碍；癫痫发作表现为局灶性发作或继发全面性发作；应用抗癫痫药物均得到有效控制。5例患儿中例1的基因变异源于父亲杂合变异，例2~5均为新发变异，分别为c.2107C>T（p.Gln703 *）无义变异、c.2284G>A（p.Gly762Arg）错义变异、c.2197del（p.Ala733Glnfs *3）移码变异、c.2511G>A（p.Trp837 *）无义变异、c.1651+1G>C剪切位点变异。经查阅文献，5例的基因变异位点均未见相关报道。 结论:癫痫失语疾病谱是一种起病复杂的癫痫综合征，不同基因变异位点可能有不同表型，发作形式以局灶性发作为主，部分可继发全面性发作，应用抗癫痫药物能够有效控制发作。 GRIN2A基因变异为癫痫失语疾病谱的遗传学病因。

abstractsObjective:To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing. Methods:The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University, from February 2019 to November 2022 were retrospectively analyzed. Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant. The characteristics of the GRIN2A gene variants were analyzed. Results:Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants, the male-to-female ratio was 4∶1, and the age range of onset was 1.5-4.4 years. The clinical phenotype included seizures in all cases, language and intellectual developmental deficits in 4 cases, and attention deficit hyperactivity disorder in 3 cases. The seizures were manifested as focal seizures or secondary generalized seizures, and were effectively controlled with antiepileptic drugs. Among the 5 children, gene variant of case 1 was originated from a paternal heterozygous variant, and cases 2-5 had de novo variants, which were c.2107C>T (p.Gln703 *) nonsense variant, c.2284G>A (p.Gly762Arg) missense variant, c.2197del (p.Ala733Glnfs *3) shifted coding variant, c.2511G>A (p.Trp837 *) nonsense variant, and c.1651+1G>C shear site variant, respectively. None of the 5 loci were reported in the literature. Conclusions:Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset, and may have different phenotypes at different genetic variant loci, with focal seizures or secondary generalized seizures, which can be effectively controlled with anti-seizure medication. The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.