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Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy

Lookup NU author(s): Professor Rita HorvathORCiD, Dr Helen Tuppen, Professor Gavin Hudson, Dr Angela Pyle, Dr Paul Smith, Professor Bobby McFarlandORCiD, Professor Zofia Chrzanowska-LightowlersORCiD, Professor Robert Lightowlers, Professor Hanns Lochmuller, Professor Robert Taylor, Professor Patrick Chinnery


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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-tRNA(Glu) 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 tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Publication metadata

Author(s): Horvath R, Kemp JP, Tuppen HAL, Hudson G, Oldfors A, Marie SKN, Moslemi AR, Servidei S, Holme E, Shanske S, Kollberg G, Jayakar P, Pyle A, Marks HM, Holinski-Feder E, Scavina M, Walter MC, Coku J, Gunther-Scholz A, Smith PM, McFarland R, Chrzanowska-Lightowlers ZMA, Lightowlers RN, Hirano M, Lochmuller H, Taylor RW, Chinnery PF, Tulinius M, DiMauro S

Publication type: Article

Publication status: Published

Journal: Brain

Year: 2009

Volume: 132

Issue: 11

Pages: 3165-3174

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press


DOI: 10.1093/brain/awp221


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Funder referenceFunder name
Academy of Medical Sciences
Marriott Mitochondrial Disorders Clinical Research Fund (MMDCRF)
Medical Research Council (UK)
UK Parkinson's Disease Society
United Mitochondrial Diseases Foundation
01GM0601German ministry of education and research (BMBF, Bonn, Germany)
074454/Z/04/ZWellcome Trust
HO 2505/2-1Deutsche Forschungsgemeinschaft
RES0211/7262RVI/NGH and Newcastle upon Tyne Hospitals NHS Charity
S1German ministry of education and research (BMBF, Bonn, Germany)