Further pitfalls in the diagnosis of mtDNA mutations: homoplasmic mt-tRNA mutations

Journal of Medical Genetics
Helen TuppenRobert W Taylor

Abstract

Mitochondrial DNA (mtDNA) mutations are important causes of human genetic disease, with mutations in tRNA genes particularly prevalent. In many patients, mutations are heteroplasmic, affecting a population of mtDNA molecules. Establishing the pathogenicity of homoplasmic mitochondrial tRNA (mt-tRNA) mutations, in which the mutation is present in every mtDNA molecule, is extremely difficult. These mutations must conform to specific pathogenic criteria, documenting unequivocally a functional defect of the mutant mt-tRNA. To investigate the pathogenic nature of two homoplasmic mt-tRNA(Thr) deletions, m.15940delT (previously reported as pathogenic) and m.15937delA, by assessing the steady state levels of the mutant mt-tRNA in tissue and cell-line samples from six unrelated families, in which affected individuals were thoroughly investigated for mitochondrial DNA disease on the basis of clinical presentations. Rates of de novo mitochondrial protein synthesis were also examined in control and m.15937delA mutant fibroblasts. Our data strongly suggest that both single nucleotide deletions are neutral polymorphisms; no obvious defects were apparent in either steady state mt-tRNA(Thr) levels or rates of mitochondrial protein synthesis. T...Continue Reading

Citations

Apr 1, 1980·Social Science & Medicine. Medical Anthropology·J Mulholland
Mar 2, 2012·European Journal of Human Genetics : EJHG·Helen A L TuppenRobert McFarland
Sep 2, 2009·Brain : a Journal of Neurology·Rita HorvathSalvatore DiMauro
Jan 27, 2012·Science Translational Medicine·Sarah E CalvoVamsi K Mootha
May 3, 2011·PLoS Genetics·Raquel Moreno-LoshuertosJosé Antonio Enríquez
Oct 20, 2012·Genetics and Molecular Research : GMR·M C ChienS W Weng
May 20, 2008·QJM : Monthly Journal of the Association of Physicians·A M HallM R Duchen
Sep 1, 2009·Expert Opinion on Medical Diagnostics·Michelangelo MancusoGabriele Siciliano
May 15, 2012·Human Mutation·Joanna L ElsonRobert McFarland
Sep 19, 2009·Biochimica Et Biophysica Acta·Helen A L TuppenRobert W Taylor

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