Journal Article

Molecular basis of infantile reversible cytochrome <i>c</i> oxidase deficiency myopathy

Rita Horvath, John P. Kemp, Helen A. L. Tuppen, Gavin Hudson, Anders Oldfors, Suely K. N. Marie, Ali-Reza Moslemi, Serenella Servidei, Elisabeth Holme, Sara Shanske, Gittan Kollberg, Parul Jayakar, Angela Pyle, Harold M. Marks, Elke Holinski-Feder, Mena Scavina, Maggie C. Walter, Jorida Çoku, Andrea Günther-Scholz, Paul M. Smith, Robert McFarland, Zofia M. A. Chrzanowska-Lightowlers, Robert N. Lightowlers, Michio Hirano, Hanns Lochmüller, Robert W. Taylor, Patrick F. Chinnery, Mar Tulinius and Salvatore DiMauro

in Brain

Published on behalf of The Guarantors of Brain

Volume 132, issue 11, pages 3165-3174
Published in print November 2009 | ISSN: 0006-8950
Published online August 2009 | e-ISSN: 1460-2156 | DOI: https://dx.doi.org/10.1093/brain/awp221

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Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as ‘benign cytochrome c oxidase deficiency myopathy’ is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNAGlu mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNAGlu may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Keywords: mitochondrial myopathy; reversible COX deficiency; homoplasmic tRNA mutation

Journal Article.  4807 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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