ASSOCIATION OF MYOPATHY WITH LARGE-SCALE MITOCHONDRIAL-DNA DUPLICATIONS AND DELETIONS - WHICH IS PATHOGENIC

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rear rangements in a 50-year-old woman with an adult-onset progressive myop athy, The predominant mtDNA abnormality was a 21.2-kb duplicated molec ule, In addition, a small population of the corresponding partially de leted 4.6-kb molecule was detected, Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase ch ain reaction analysis, COX-negative fibers contained a low number of w ild-type or duplicated mtDNA molecules tie, nondeleted). In situ hybri dization demonstrated that the abnormal fibers contained increased amo unts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primaril y responsible for the phenotype in this patient.