|Title||Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies.|
|Publication Type||Journal Article|
|Year of Publication||1991|
|Authors||Servidei, S, Zeviani, M, Manfredi, G, Ricci, E, Silvestri, G, Bertini, E, Gellera, C, Di Mauro, S, Di Donato, S, Tonali, P|
|Date Published||1991 Jul|
|Keywords||Adult, Chromosome Deletion, DNA, Mitochondrial, Female, Genes, Dominant, Humans, Male, Middle Aged, Mitochondria, Muscle, Muscles, Muscular Diseases, Pedigree, Polymerase Chain Reaction|
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.