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.
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