Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies.
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.
Servidei
S
S
Neurological Institute, Università Cattolica, Rome, Italy.
Zeviani
M
M
Manfredi
G
G
Ricci
E
E
Silvestri
G
G
Bertini
E
E
Gellera
C
C
Di Mauro
S
S
Di Donato
S
S
Tonali
P
P
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
D004272:DNA, Mitochondrial