摘要目的:探讨1例癫痫性脑病(DEE)患儿的临床表型及遗传学病因。方法:收集2021年2月就诊于广东医科大学附属医院儿童医学中心的1例患儿的临床资料进行回顾性分析。采集患儿及其父母的外周血样，对其进行全外显子组测序，对候选变异进行Sanger测序验证。以" ATP6V0A1基因""发育性及癫痫性脑病104型"" ATP6V0A1 variant""developmental and epileptic encephalopathy 104""DEE 104""epileptic encephalopathy"为关键词检索中国知网、万方数据平台以及PubMed数据库中的相关文献，检索时间为建库至2022年12月。 结果:患儿为5月龄男性，婴儿期起病，表现为频繁的局灶性发作，伴严重发育落后，体型消瘦、小头畸形、外眦上斜，精灵耳，四肢肌张力低下。患儿脑电图提示多灶性尖波、慢波、棘慢波发放，头颅MRI发现双侧侧脑室、第三脑室扩大，脑沟、脑裂、脑池增宽。测序结果提示患儿 ATP6V0A1基因存在c.2401C>T(p.His801Tyr)新发错义变异，判读为可能致病性(PS2＋PM2_Supporting＋PP3)。结合患儿的临床表型和基因检测结果，确诊其为DEE104型。共检索到 ATP6V0A1基因变异所致DEE104型文献2篇，共14例。DEE104型患者变异以杂合变异为主，热点变异为c.2219G>A(10/14, 71.4%)，最常见的临床特征为难治性癫痫发作及发育迟缓(14/14, 100.0%)。 结论:患儿考虑为 ATP6V0A1基因c.2401C>T的杂合变异所致的癫痫型脑病104型。

abstractsObjective:To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104).Methods:A child who had presented at the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl′s ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c. 2401C>T (p.His801Tyr) missense variant of the ATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy. Conclusion:The c. 2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.