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• W2105375495 endingPage "2242" @default.
• W2105375495 startingPage "2239" @default.
• W2105375495 abstract "Replicative segregation of mitochondrial DNA (mtDNA) can produce large differences in the proportions of wild-type and mutant mtDNAs in different cell types of patients with mitochondrial encephalomyopathy. This is particularly striking in the skeletal muscle of patients with Kearns-Sayre syndrome (KSS), a sporadic disease associated with large-scale mtDNA deletions, and in sporadic patients with tRNA point mutations. Although the skeletal muscle fibres of these patients invariably contain a large proportion of mutant mtDNAs, mutant mtDNAs are rare or undetectable in satellite cells cultured from the same muscle biopsy specimens. Since satellite cells are responsible for muscle fibre regeneration, restoration of the wild-type mtDNA genotype might be achieved in these patients by encouraging muscle regeneration. To test this concept, we re-biopsied a patient with a KSS phenotype and a mtDNA point mutation in the tRNAleu(CUN) gene and analysed muscle fibres regenerating at the site of the original muscle biopsy. Regenerating fibres were identified by morphological criteria and by expression of neural cell adhesion molecule (NCAM). All such fibers were positive for cytochrome c oxidase (COX) activity by cytochemistry and essentially homoplasmic for wild-type mtDNA, while the majority of non-regenerating fibres were COX-negative and contained predominantly mutant mtDNAs. These results demonstrate that it may be possible to improve muscle function in similar patients by methods that promote satellite cell incorporation into existing myofibres." @default.
• W2105375495 created "2016-06-24" @default.
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• W2105375495 date "1997-12-01" @default.
• W2105375495 modified "2023-09-26" @default.
• W2105375495 title "Complete restoration of a wild-type mtDNA genotype in regenerating muscle fibres in a patient with a tRNA point mutation and mitochondrial encephalomyopathy" @default.
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• W2105375495 doi "https://doi.org/10.1093/hmg/6.13.2239" @default.
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