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氨酰基-tRNA合成酶基因变异10例分析
吴腾辉, 彭镜, 张慈柳, 吴丽文, 杨丽芬, 彭盼, 庞楠, 尹飞, 何芳
中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (6) : 595-601.
PDF(2071 KB)
PDF(2071 KB)
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
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.
氨酰基-tRNA合成酶缺陷 / ARS2/ARS基因 / 儿童
Aminoacyl-tRNA synthetases deficiency / ARS/ARS2 gene / Child
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