Co-existence of high levels of a cytochrome b mutation and of a tandem 200 bp duplication in the D-loop of muscle human mitochondrial DNA

Previous studies have suggested that some patients with large-scalemitochondrial DNA (mtDNA) deletions also presented a heteroplasmic 260 bptandem duplication in the mtDNA D-loop region. Such duplications wereobserved not only in patients with mitochondrial pathology but also in agedsubjects. However, the percentage of duplicated mtDNA did not exceed a fewper cent of the total mtDNA, except in one example where it reached 30%. Wereport here another type of 200 bp duplication in the mtDNA D-loop regionthat, instead of being associated with a large-scale deletion, iscorrelated to the presence of a point mutation in the cytochrome b gene.The 200 bp duplication concerned up to 95% of the total mtDNA of somemuscle mitochondria and was absent from the patient lymphocyte DNA. Thepercentages of the 200 bp duplication and that of the cytochrome b mutationwere relatively close in whole muscle as well as in single muscle fibres,suggesting a correlation between the mutation and the duplication. Thisduplication could also be detected by PCR in two other patients withmitochondrial disorders but without known deletion or mtDNA mutation. Thesedata suggest that the accumulation of these small duplications in the mtDNAD-loop could be indicative of the presence of other defects of the mtDNAwhich would damage the respiratory chain function. These deficiencies wouldinduce the generation of small duplications in the D-loop.