Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5500973 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2017 | 28 Pages |
Abstract
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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Authors
Michela Di Nottia, Arianna Montanari, Daniela Verrigni, Romina Oliva, Alessandra Torraco, Erika Fernandez-Vizarra, Daria Diodato, Teresa Rizza, Marzia Bianchi, Michela Catteruccia, Massimo Zeviani, Carlo Dionisi-Vici, Silvia Francisci, Enrico Bertini,