biostudies-literatureJin DNIGMS NIH HHS358-363https://www.ebi.ac.uk/biostudies/studies/S-EPMC9898101biostudies-literatureUnknown103(3)Aminoacyl-tRNA synthetases are enzymes that ensure accurate protein synthesis. Variants of the dual-functional cytoplasmic human glutamyl-prolyl-tRNA synthetase, EPRS1, have been associated with leukodystrophy, diabetes and bone disease. Here, we report compound heterozygous variants in EPRS1 in a 4-year-old female patient presenting with psychomotor developmental delay, seizures and deafness. Functional studies of these two missense mutations support major defects in enzymatic function in vitro and contributed to confirmation of the diagnosis.Clinical geneticsAminoacylation-defective bi-allelic mutations in human EPRS1 associated with psychomotor developmental delay, epilepsy, and deafness.PMC9898101R35 GM141880R35 GM136331Lacombe DWek RCMusier-Forsyth KJin DWek SAMichaud VCordova RAfalseAminoacylation-defective bi-allelic mutations in human EPRS1 associated with psychomotor developmental delay, epilepsy, and deafness.Aminoacyl-tRNA synthetases are enzymes that ensure accurate protein synthesis. Variants of the dual-functional cytoplasmic human glutamyl-prolyl-tRNA synthetase, EPRS1, have been associated with leukodystrophy, diabetes and bone disease. Here, we report compound heterozygous variants in EPRS1 in a 4-year-old female patient presenting with psychomotor developmental delay, seizures and deafness. Functional studies of these two missense mutations support major defects in enzymatic function in vitro and contributed to confirmation of the diagnosis.2023-01-01T00:00:00Z2023 Mar2026-03-27T15:48:50.255Z2025-02-19T01:42:16.049ZS-EPMC98981013641195510.1111/cge.14269