In situ hybridization of mitochondrial DNA in the heart of a patient with Kearns-Sayre syndrome and dilatative cardiomyopathy.
Previous studies have revealed cytochrome-c-oxidase-deficient cardiomyocytes and the 4,977 base pair deletion ("common deletion") of mitochondrial DNA (position 8,482-13,459) in the heart of a patient with dilatative cardiomyopathy and Kearns-Sayre syndrome. In the present investigation the co-localization of the enzymatic and genomic defects was studied. In situ hybridization of mitochondrial DNA (mtDNA) revealed different hybridization patterns in the cytochrome-c-oxidase-deficient cells: (1) a selective reduction of the hybridization signal with an mtDNA probe recognizing the common deletion, indicating predominance of the deleted over the nondeleted mtDNA molecules in the cytochrome-c-oxidase-deficient cells; (2) a reduced hybridization signal with different mtDNA probes, indicating depletion of mtDNA; and (3) normal hybridization signals with different probes in single cytochrome-c-oxidase-deficient cardiomyocytes. These results indicate that different mechanisms may co-exist in Kearns-Sayre syndrome and may lead to defective respiratory chain function. The question of the pathogenetic interrelationship is discussed.
Müller-Höcker
J
J
Institute of Pathology, University of Munich, Germany.
Seibel
P
P
Schneiderbanger
K
K
Zietz
C
C
Obermaier-Kusser
B
B
Gerbitz
K D
KD
Kadenbach
B
B
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015342:DNA Probes; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000032:analysis; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007625:Kearns-Sayre Syndrome / Q000235:genetics* / Q000473:pathology; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology / Q000648:ultrastructure; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure
D015342:DNA Probes; D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV