Families of mtDNA re-arrangements can be detected in patients with mtDNA deletions: duplications may be a transient intermediate form.

In three patients with mitochondrial DNA duplications, there are two additional re-arranged molecules derived from mitochondrial DNA. Two forms of closed circular deletions of mitochondrial DNA have been characterised in all three patients, one being a monomer, and the other a dimer. The junction fragments appear to be the same in the deletion and the duplication, suggesting that both re-arrangements arose from the same initial recombination event, followed by homologous recombination. Sequential muscle biopsy and cell culture studies suggest that the duplication is present only transiently in muscle and cloned fibroblast lines. The duplicated molecule could thus be an intermediate in the formation of the deletion. Evidence is presented for the presence of duplicated mtDNA in 6/11 patients known to have deletions of mitochondrial DNA in muscle, suggesting that this could be a general mechanism for major re-arrangements of mitochondrial DNA. There may be parallels between the families of re-arrangements found in plant mitochondrial DNA, and the three distinct re-arranged molecules described here.