biostudies-literatureZhang SNatural Science Foundation of China376https://www.ebi.ac.uk/biostudies/studies/S-EPMC11468052biostudies-literatureUnknown19(1)Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) reOrphanet journal of rare diseasesTARS2 c.470 C > G is a chinese-specific founder mutation in three unrelated families with mitochondrial encephalomyopathy.PMC1146805282201312, 82071276, Z-A20230362 and No. Z-A20240323Chen QHuang JKan LLai BZhang SYuan HLiu YWang QJi XGeng GLuo JQin ZWei SQin HYang QWang YShen YfalseTARS2 c.470 C > G is a chinese-specific founder mutation in three unrelated families with mitochondrial encephalomyopathy.Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) re2024-01-01T00:00:00Z2024 Oct2026-07-14T10:20:35.759Z2025-04-04T01:24:35.8ZS-EPMC114680523939413810.1186/s13023-024-03365-w