ATP1A3基因相关发作性疾病的临床特征及基因变异分析  

Clinical characteristics and mutation analysis of ATP1A3 gene associated paroxysmal diseases

作　　者：孙于林 杨光[1] 万林 李志超[1] 张凡 王静[1] 石秀玉[1] 邹丽萍[1] SUN Yulin;YANG Guang;WAN Lin;LI Zhichao;ZHANG Fan;WANG Jing;SHI Xiuyu;ZOU Liping(Department of Pediatric,First Medical Center of Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心儿内科,北京100853

出　　处：《临床儿科杂志》2020年第11期817-820,共4页Journal of Clinical Pediatrics

基　　金：国家自然科学基金面上项目(No.81671279);解放军总医院医疗大数据与人工智能研发项目(No.2019MBD-004)。

摘　　要：目的总结ATP1A3基因相关发作性疾病的临床特征,探讨表型与基因型的关联。方法回顾性分析2018年9月至2019年12月收治的4例ATP1A3基因变异相关发作性疾病患儿的临床资料及基因检测结果。结果4例患儿均为男性,中位起病年龄5个月(20日龄~9月龄);临床诊断分别为儿童交替性偏瘫(AHC),AHC并癫痫,癫痫和小脑性共济失调、反射消失、高弓足、视神经萎缩和感觉神经性听力减退(CAPOS)。患儿首发症状和临床表现各不相同,又有重叠相似之处。所有患儿均存在ATP1A3基因杂合变异,共发现4种错义变异;3例为新发变异,1例来源于其母亲。除外c.2423C>T,p.P808L未见报道,其余3种(c.2839G>C,p.G 947R;c.2401G>A,p.D 801N;c.2452G>A,p.E 818K)均为已报道的致病性变异。结论ATP1A3基因变异可引起AHC、CAPOS综合征、癫痫等不同临床表型,c.2423C>T,p.P808L为新发现的致病性变异。Objective To summarize the clinical characteristics of ATP1A3 gene associated paroxysmal diseases,and to explore clinical phenotype and genotype relationship.Methods Clinical data and genetic test results of four children with ATP1A3 gene associated paroxysmal diseases recruited from September,2018 to December,2019 were retrospectively analyzed.Results Four male patients were recruited.The median age of onset was 5 months(ranged from 20 days to 9 months).Clinical phenotypes of the four children were alternating hemiplegia of children(AHC),AHC with epilepsy,epilepsy,and CAPOS(cerebellar ataxia,areflexia,pes cavus,opticatrophy,and sensorineural hearing loss)syndrome respectively.The initial symptoms and clinical manifestations were different,but there was some overlap.All four children were found with heterozygous mutations in the ATP1A3 gene,including three de novo and one maternal inherited missense mutation.Among which,c.2423C>T,has not been reported,and c.2839 G>C,c.2401G>A and c.2452G>A are reported as pathogenic mutations.Conclusions ATP1A3 gene mutations can cause different clinical phenotypes such as AHC,CAPOS syndrome and epilepsy.c.2423C>T,is a novel pathogenic mutation that has not been reported.

关 键 词：ATP1A3基因 CAPOS综合征 儿童交替性偏瘫 癫痫 

分 类 号：R748[医药卫生—神经病学与精神病学]