title: In situ hybridization of mitochondrial DNA in the heart of a patient with Kearns-Sayre syndrome and dilatative cardiomyopathy.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: P
authors.initials: P
authors.lastname: Seibel
authors.forename: K
authors.initials: K
authors.lastname: Schneiderbanger
authors.forename: C
authors.initials: C
authors.lastname: Zietz
authors.forename: B
authors.initials: B
authors.lastname: Obermaier-Kusser
authors.forename: K D
authors.initials: KD
authors.lastname: Gerbitz
authors.forename: B
authors.initials: B
authors.lastname: Kadenbach
mesh_terms: 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
chemical_list: D015342:DNA Probes; D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV