title: Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies.
abstract: We studied a large family with a dominantly inherited mitochondrial myopathy characterized by progressive external ophthalmoplegia, dysphagia, cataract, lactic acidosis, exercise intolerance, and early death. Morphologic studies of muscle biopsies suggested mitochondrial heteroplasmy and revealed ragged-red fibers and decreased histochemical reactions for cytochrome c oxidase and succinate dehydrogenase. Biochemistry showed a partial defect of cytochrome c oxidase and a mild generalized reduction of other mitochondrial enzymes requiring mitochondrial DNA-encoded subunits. Southern blot analysis and PCR amplification showed mitochondrial DNA deletions in muscle of all affected members, but not in lymphocytes or fibroblasts, suggesting a tissue-specific distribution. Deletions were multiple and seemed to increase with time and to correlate with the severity of the disease.
authors.affiliation: Neurological Institute, Università Cattolica, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Servidei
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
authors.forename: G
authors.initials: G
authors.lastname: Manfredi
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: C
authors.initials: C
authors.lastname: Gellera
authors.forename: S
authors.initials: S
authors.lastname: Di Mauro
authors.forename: S
authors.initials: S
authors.lastname: Di Donato
authors.forename: P
authors.initials: P
authors.lastname: Tonali
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial