Mutations in aminoacyl-tRNA synthetase genes: an analysis of 10 cases.
- Author:
Teng-Hui WU
1
;
Jing PENG
;
Ci-Liu ZHANG
;
Li-Wen WU
;
Li-Fen YANG
;
Pan PENG
;
Nan PANG
;
Fei YIN
;
Fang HE
Author Information
1. Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, China. bubbly_ho@163.com.
- Publication Type:Journal Article
- MeSH:
Amino Acyl-tRNA Synthetases;
genetics;
Child;
Epilepsy;
Humans;
Mutation;
Phenotype;
Retrospective Studies
- From:
Chinese Journal of Contemporary Pediatrics
2020;22(6):595-601
- CountryChina
- Language:Chinese
-
Abstract:
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.
