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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Pub. Co 2017
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.
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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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