Abstract
Although mutations in mitochondrial tRNAs constitute the most common mtDNA defect, the presence of pathological variants in mitochondrial tRNAAsn is extremely rare. We were able to identify a novel mtDNA tRNAAsn gene pathogenic mutation associated with a myopathic phenotype and a previously unreported respiratory impairment. Our proband is an adult woman with ophthalmoparesis and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX−) fibres and signs of mitochondrial proliferation (ragged red fibres). Sequence analysis of the muscle-derived mtDNA revealed an m.5709T>C substitution, affecting mitochondrial tRNAAsn gene. Restriction-fragment length polymorphism analysis of the mutation in isolated muscle fibres showed that a threshold of at least 91.9% mutated mtDNA results in the COX deficiency phenotype. The new phenotype further increases the clinical spectrum of mitochondrial diseases caused by mutations in the tRNAAsn gene.
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Acknowledgements
Gratitude has to be expressed to the patient for participating in this research. We wish to thank especially the ‘Associazione Amici del Centro Dino Ferrari’ for their support. The financial support of the following research grant is gratefully acknowledged: Telethon – UILDM Project GUP09004 ‘Construction of a database for a nation-wide Italian collaborative network of mitochondrial diseases’, Associazione Amici del Centro Dino Ferrari, University of Milan, the Telethon project GTB07001, the Eurobiobank project QLTR-2001-02769 and RF 02.187 Criobanca Automatizzata di Materiale Biologico.
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Ronchi, D., Sciacco, M., Bordoni, A. et al. The novel mitochondrial tRNAAsn gene mutation m.5709T>C produces ophthalmoparesis and respiratory impairment. Eur J Hum Genet 20, 357–360 (2012). https://doi.org/10.1038/ejhg.2011.238
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DOI: https://doi.org/10.1038/ejhg.2011.238
