A mitochondrial DNA duplication as a marker of skeletal muscle specific mutations in the mitochondrial genome

[eng] Mitochondrial myopathies are often associated with point mutations in mitochondrial DNA (mtDNA), and are usually maternally inherited. However, they may also present as an isolated myopathy, often with ptosis and ophthalmoparesis,1 or with isolated exercise intolerance.2 In eight patients with exercise intolerance described by us in 1999,2 there was no evidence of maternal inheritance, muscle histochemistry showed cytochrome c oxidase (COX) positive ragged red fibres, biochemistry showed complex III deficiency, and molecular genetic analysis revealed different mutations in the mitochondrial cytochrome b gene (CYB). Several other patients with lifelong exercise intolerance harboured mutations in other mtDNA protein coding genes.3 Characteristically, these mutations are not maternally inherited and are abundant (more than 90%) in skeletal muscle, where they coexist with smaller amounts of wild type mtDNA genomes. As a rule, the mutations are not present in other tissues and, surprisingly, are not found in cultured myoblasts, indicating that they are somatic mutations of skeletal muscle. However, the mechanism by which these mutations accumulate in muscle remains unknown