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Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation
The mitochondrial Elongation Factor Tu (EF-Tu), encoded by the TUFM gene, is a highly conserved GTPase, which is part of the mitochondrial protein translation machinery. In its activated form it delivers the aminoacyl-tRNAs to the A site of the mitochondrial ribosome. We report here on a baby girl w...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Pub. Co
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335904/ https://www.ncbi.nlm.nih.gov/pubmed/28132884 http://dx.doi.org/10.1016/j.bbadis.2017.01.022 |
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author | Di Nottia, Michela Montanari, Arianna Verrigni, Daniela Oliva, Romina Torraco, Alessandra Fernandez-Vizarra, Erika Diodato, Daria Rizza, Teresa Bianchi, Marzia Catteruccia, Michela Zeviani, Massimo Dionisi-Vici, Carlo Francisci, Silvia Bertini, Enrico Carrozzo, Rosalba |
author_facet | Di Nottia, Michela Montanari, Arianna Verrigni, Daniela Oliva, Romina Torraco, Alessandra Fernandez-Vizarra, Erika Diodato, Daria Rizza, Teresa Bianchi, Marzia Catteruccia, Michela Zeviani, Massimo Dionisi-Vici, Carlo Francisci, Silvia Bertini, Enrico Carrozzo, Rosalba |
author_sort | Di Nottia, Michela |
collection | PubMed |
description | The mitochondrial Elongation Factor Tu (EF-Tu), encoded by the TUFM gene, is a highly conserved GTPase, which is part of the mitochondrial protein translation machinery. In its activated form it delivers the aminoacyl-tRNAs to the A site of the mitochondrial ribosome. We report here on a baby girl with severe infantile macrocystic leukodystrophy with micropolygyria and a combined defect of complexes I and IV in muscle biopsy, caused by a novel mutation identified in TUFM. Using human mutant cells and the yeast model, we demonstrate the pathological role of the novel variant. Moreover, results of a molecular modeling study suggest that the mutant is inactive in mitochondrial polypeptide chain elongation, probably as a consequence of its reduced ability to bind mitochondrial aa-tRNAs. Four patients have so far been described with mutations in TUFM, and, following the first description of the disease in a single patient, we describe similar clinical and neuroradiological features in an additional patient. |
format | Online Article Text |
id | pubmed-5335904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier Pub. Co |
record_format | MEDLINE/PubMed |
spelling | pubmed-53359042017-04-01 Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation Di Nottia, Michela Montanari, Arianna Verrigni, Daniela Oliva, Romina Torraco, Alessandra Fernandez-Vizarra, Erika Diodato, Daria Rizza, Teresa Bianchi, Marzia Catteruccia, Michela Zeviani, Massimo Dionisi-Vici, Carlo Francisci, Silvia Bertini, Enrico Carrozzo, Rosalba Biochim Biophys Acta Article The mitochondrial Elongation Factor Tu (EF-Tu), encoded by the TUFM gene, is a highly conserved GTPase, which is part of the mitochondrial protein translation machinery. In its activated form it delivers the aminoacyl-tRNAs to the A site of the mitochondrial ribosome. We report here on a baby girl with severe infantile macrocystic leukodystrophy with micropolygyria and a combined defect of complexes I and IV in muscle biopsy, caused by a novel mutation identified in TUFM. Using human mutant cells and the yeast model, we demonstrate the pathological role of the novel variant. Moreover, results of a molecular modeling study suggest that the mutant is inactive in mitochondrial polypeptide chain elongation, probably as a consequence of its reduced ability to bind mitochondrial aa-tRNAs. Four patients have so far been described with mutations in TUFM, and, following the first description of the disease in a single patient, we describe similar clinical and neuroradiological features in an additional patient. Elsevier Pub. Co 2017-04 /pmc/articles/PMC5335904/ /pubmed/28132884 http://dx.doi.org/10.1016/j.bbadis.2017.01.022 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Di Nottia, Michela Montanari, Arianna Verrigni, Daniela Oliva, Romina Torraco, Alessandra Fernandez-Vizarra, Erika Diodato, Daria Rizza, Teresa Bianchi, Marzia Catteruccia, Michela Zeviani, Massimo Dionisi-Vici, Carlo Francisci, Silvia Bertini, Enrico Carrozzo, Rosalba Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation |
title | Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation |
title_full | Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation |
title_fullStr | Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation |
title_full_unstemmed | Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation |
title_short | Novel mutation in mitochondrial Elongation Factor EF-Tu associated to dysplastic leukoencephalopathy and defective mitochondrial DNA translation |
title_sort | novel mutation in mitochondrial elongation factor ef-tu associated to dysplastic leukoencephalopathy and defective mitochondrial dna translation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335904/ https://www.ncbi.nlm.nih.gov/pubmed/28132884 http://dx.doi.org/10.1016/j.bbadis.2017.01.022 |
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