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Association of myopathy with large‐scale mitochondrial dna duplications and deletions: Which is pathogenic?
Author(s) -
Manfredi Giovanni,
Vu Tuan,
Bonilla Eduardo,
Schon Eric A.,
DiMauro Salvatore,
Arnaudo Enrica,
Zhang Lee,
Rowland Lewis P.,
Hirano Michio
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410420208
Subject(s) - mitochondrial dna , mitochondrial myopathy , genetics , association (psychology) , myopathy , biology , gene , psychology , psychotherapist
We identified large‐scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50–year‐old woman with an adult‐onset progressive myopathy. The predominant mtDNA abnormality was a 21.2–kb duplicated molecule. In addition, a small population of the corresponding partially deleted 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 chain reaction analysis, COX‐negative fibers contained a low number of wild‐type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.