氨酰基-tRNA合成酶基因变异10例分析  

Mutations in aminoacyl-tRNA synthetase genes:an analysis of 10 cases

作　　者：吴腾辉 彭镜[1,2] 张慈柳 吴丽文[1,2] 杨丽芬 彭盼[1,2] 庞楠 尹飞[1,2] 何芳 WU Teng-Hui;PENG Jing;ZHANG Ci-Liu;WU Li-Wen;YANG Li-Fen;PENG Pan;PANG Nan;YIN Fei;HE Fang(Department of Pediatrics,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院儿科,湖南长沙410008 [2]湖南省儿童智力障碍研究中心,湖南长沙410008

出　　处：《中国当代儿科杂志》2020年第6期595-601,共7页Chinese Journal of Contemporary Pediatrics

摘　　要：目的研究氨酰基-tRNA合成酶(ARS)缺陷相关疾病的临床特征。方法回顾性分析2016年1月至2019年10月通过二代测序诊断的10例ARS基因变异患儿的临床资料及基因突变类型。结果 10例ARS基因变异患儿中,起病年龄为0~9岁,首发症状多为抽搐(7例)。临床表现为共济失调为主而智力轻度落后或正常,伴或不伴有癫痫(4例);或儿童期起病的癫痫,后出现发育倒退(2例);也可表现为新生儿期起病,严重癫痫脑病,出现肌阵挛、全面强直及痉挛发作(4例),伴有严重发育落后(3例)、喂养困难(2例)、听力损害(1例)等。10例患儿中,共检测出5种基因突变,包括AARS2(c.331G>C、c.2682+5G>A、c.2164C>T、c.761G>A,均为新突变)3例,DARS2(c.228-16C>A、c.536G>A,均为已报道突变)2例,CARS2(c.1036C>T、c.323T>G,均为新突变)1例,RARS2(c.1210A>G、c.622C>T,均为新突变)1例,AARS(c.1901T>A、c.229C>T、c.244C>T、c.961G>C、Chr16:70298860-70316687del、c.2248C>T,均为新突变)3例。结论 ARS基因缺陷相关疾病临床表型异质性高。该研究共发现5种ARS基因的14个未报道的变异,丰富了ARS缺陷相关疾病的临床表型及基因型。Objective To study the clinical features of the diseases associated with aminoacyl-tRNA synthetases(ARS)deficiency.Methods A retrospective analysis was performed of the clinical and gene mutation data of 10 children who were diagnosed with ARS gene mutations,based on next-generation sequencing from January 2016 to October 2019.Results The age of onset ranged from 0 to 9 years among the 10 children.Convulsion was the most common initial symptom(7 children).Clinical manifestations included ataxia and normal or mildly retarded intellectual development(with or without epilepsy;n=4)and onset of epilepsy in childhood with developmental regression later(n=2).Some children experienced disease onset in the neonatal period and had severe epileptic encephalopathy,with myoclonus,generalized tonic-clonic seizure,and convulsive seizure(n=4);3 had severe delayed development,2 had feeding difficulty,and 1 had hearing impairment.Mutations were found in five genes:3 had novel mutations in the AARS2 gene(c.331G>C,c.2682+5G>A,c.2164C>T,and c.761G>A),2 had known mutations in the DARS2 gene(c.228-16C>A and c.536G>A),1 had novel mutations in the CARS2 gene(c.1036C>T and c.323T>G),1 had novel mutations in the RARS2 gene(c.1210A>G and c.622C>T),and 3 had novel mutations in the AARS gene(c.1901T>A,c.229C>T,c.244C>T,c.961G>C,c.2248C>T,and Chr16:70298860-70316687del).Conclusions A high heterogeneity is observed in the clinical phenotypes of the diseases associated with the ARS deficiency.A total of 14 novel mutations in 5 genes are reported in this study,which enriches the clinical phenotypes and genotypes of the diseases associated with ARS deficiency.

关 键 词：氨酰基-tRNA合成酶缺陷 ARS2/ARS基因 儿童 

分 类 号：R725.9[医药卫生—儿科]