Analysis of mtDNA deletions in muscle by in situ hybridization.
We compared the distribution of deleted mitochondrial DNA (Delta-mtDNA) in skeletal muscle of a patient with autosomal recessive (AR) and another with autosomal dominant (AD) progressive external ophthalmoplegia (PEO) by in situ hybridization (ISH). The patients studied had similar numbers of fibers deficient in cytochrome c oxidase (COX) activity (13.6% and 12.8%) and fibers with mitochondrial proliferation (5.5% and 5.3%). ISH suggested that each COX-deficient fiber contained a single species of Delta-mtDNA. Most deletions ablated the region between the genes encoding adenosine triphosphate (ATP) synthase subunit 8 and cytochrome b. Fibers that appeared to be depleted of mtDNA were also present. We conclude that muscle from patients with autosomally inherited PEO contains not only Delta-mtDNA but also focal depletion of mtDNA and that the distribution of these mtDNA defects appears to be similar. These changes most likely represent the common consequence of whatever genetic factors are responsible for the generation of Delta-mtDNA.
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H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, College of Physicians & Surgeons, 5-431, 630 West 168th Street, Columbia University, New York, New York 10032, USA.
Tanji
K
K
Pallotti
F
F
Golzi
V
V
Hirano
M
M
DiMauro
S
S
Bonilla
E
E
D000328:Adult; D015139:Blotting, Southern; D002648:Child; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000737:chemistry*; D018482:Muscle, Skeletal / Q000737:chemistry*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism
D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV