期刊
BRAIN
卷 132, 期 -, 页码 3165-3174出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awp221
关键词
mitochondrial myopathy; reversible COX deficiency; homoplasmic tRNA mutation
资金
- Deutsche Forschungsgemeinschaft [HO 2505/2-1]
- Academy of Medical Sciences
- RVI/NGH and Newcastle upon Tyne Hospitals NHS Charity [RES0211/7262]
- Wellcome Trust [074454/Z/04/Z]
- BBSRC [BB/F011520/1]
- United Mitochondrial Diseases Foundation
- Medical Research Council (UK)
- UK Parkinson's Disease Society
- UK NIHR
- German ministry of education and research (BMBF, Bonn, Germany) [S1, 01GM0601]
- NIH [HD32062]
- Marriott Mitochondrial Disorders Clinical Research Fund (MMDCRF)
- [7122]
- Biotechnology and Biological Sciences Research Council [BB/F011520/1] Funding Source: researchfish
- Medical Research Council [G0601943B, G0800674, G0700718B, G108/539] Funding Source: researchfish
- BBSRC [BB/F011520/1] Funding Source: UKRI
- MRC [G108/539, G0800674] Funding Source: UKRI
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.
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