{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:35:53Z","timestamp":1793338553070,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":2898,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1996,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sporadic progressive external ophthalmoplegia and Kearns\u2010Sayre syndrome are usually associated with single large\u2010scale mitochondrial DNA deletions in muscle. In progressive external ophthalmoplegia with autosomal dominant inheritance, multiple mitochondrial DNA deletions have been reported. We studied several members of a Swedish family with autosomal dominant progressive external ophthalmoplegia and multiple mitochondrial DNA deletions by polymerase chain reaction analysis of singl emuscle fibers and by in sit hybridization, combined with enzyme histochemical analysis. Muscle fiber segments with deficiency of cytochrome <jats:italic>c<\/jats:italic> oxidase, which is partially encoded by mitochondrial DNA, had accumulated mitochondrial DNA with deletions and showed reduced levels of wild\u2010type mitochondrial DNA. The deletions varied between individual muscle fibers. There was one predominant deletion in each cytochrome <jats:italic>c<\/jats:italic> oxidase\u2010deficient muscle fiber segment. Sequencing of the deletion breakpoints showed that most but not all of the deletions were flanked by direct repeats. Young, clinically affected individuals of this family without limb muscle symptoms did not show mitochondral DNA deletions or cytochorme <jats:italic>c<\/jats:italic> oxidase\u2010deficient muscle fibers. Our result indicate that a nuclear factor predisposes to the developement of somatic multiple mitochondrial DNA deletions. Mitochondrial DNA with multiple different deletions shows clonal expansion, which leads to mitochondrial myopathy with ragged\u2010red fibers and muscle weakness.<\/jats:p>","DOI":"10.1002\/ana.410400506","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T14:52:41Z","timestamp":1104591161000},"page":"707-713","source":"Crossref","is-referenced-by-count":73,"title":["Clonal expansion of mitochondrial DNA with multiple deletions in autosomal dominant progressive external 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