Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease

Wen-Qiang Zheng, Signe Vandal Pedersen, Kyle Thompson, Emanuele Bellacchio, Courtney E French, Benjamin Munro, Toni S Pearson, Julie Vogt, Daria Diodato, Tue Diemer, Anja Ernst, Rita Horvath, Manali Chitre, Jakob Ek, Flemming Wibrand, Dorothy K Grange, Lucy Raymond, Xiao-Long Zhou, Robert W Taylor, Elsebet Ostergaard

11 Citationer (Scopus)


TARS2 encodes human mitochondrial threonyl tRNA-synthetase that is responsible for generating mitochondrial Thr-tRNAThr and clearing mischarged Ser-tRNAThr during mitochondrial translation. Pathogenic variants in TARS2 have hitherto been reported in a pair of siblings and an unrelated patient with an early onset mitochondrial encephalomyopathy and a combined respiratory chain enzyme deficiency in muscle. We here report five additional unrelated patients with TARS2-related mitochondrial diseases, expanding the clinical phenotype to also include epilepsy, dystonia, hyperhidrosis and severe hearing impairment. In addition, we document seven novel TARS2 variants-one nonsense variant and six missense variants-that we demonstrate are pathogenic and causal of the disease presentation based on population frequency, homology modeling and functional studies that show the effects of the pathogenic variants on TARS2 stability and/or function.

TidsskriftHuman Molecular Genetics
Udgave nummer4
Sider (fra-til)523-534
Antal sider12
StatusUdgivet - 21 feb. 2022


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