Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease
| Autor: | Kyle Thompson, Xiao-Long Zhou, Flemming Wibrand, Wen-Qiang Zheng, Julie Vogt, Daria Diodato, Lucy Raymond, Anja Ernst, Robert W. Taylor, Emanuele Bellacchio, Rita Horvath, Jakob Ek, Benjamin Munro, Manali Chitre, Dorothy K. Grange, Tue Diemer, Elsebet Østergaard, Courtney E. French, Toni S. Pearson, Signe Vandal Pedersen |
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| Rok vydání: | 2021 |
| Předmět: |
Mitochondrial encephalomyopathy
Mitochondrial Diseases Mitochondrial translation media_common.quotation_subject Mitochondrial disease Nonsense Population Biology 03 medical and health sciences Epilepsy 0302 clinical medicine Mitochondrial Encephalomyopathies Threonine-tRNA Ligase Genetics medicine Humans Missense mutation education Molecular Biology Genetics (clinical) 030304 developmental biology media_common RNA Transfer Thr Dystonia 0303 health sciences education.field_of_study General Medicine medicine.disease Phenotype Mutation 030217 neurology & neurosurgery |
| Zdroj: | Zheng, W-Q, Pedersen, S V, Thompson, K, Bellacchio, E, French, C E, Munro, B, Pearson, T S, Vogt, J, Diodato, D, Diemer, T, Ernst, A, Horvath, R, Chitre, M, Ek, J, Wibrand, F, Grange, D K, Raymond, L, Zhou, X-L, Taylor, R W & Ostergaard, E 2022, ' Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease ', Human Molecular Genetics, vol. 31, no. 4, pp. 523-534 . https://doi.org/10.1093/hmg/ddab257 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddab257 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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