title: Different tissue distribution of a mitochondrial DNA duplication and the corresponding deletion in a patient with a mild mitochondrial encephalomyopathy: deletion in muscle, duplication in blood.
abstract: Large-scale heteroplasmic mtDNA rearrangements were identified in a 57-year-old woman with chronic depressive disorder, hearing-loss, diabetes mellitus and a slowly progressive encephalomyopathy. A high percentage of a 24.2 kb duplicated molecule was found in lymphocytes whereas the corresponding deletion dimer dominated in muscle. PCR and Southern blot analyses were used to identify a 7658 bp duplication/deletion fragment. The duplicated mtDNA disrupted the cytochrome oxidase subunit I and cytochrome b genes at a position where there were no direct repeats. Duplicated mtDNA was not observed in the mother and brother of the patient. Histochemical analysis of skeletal muscle demonstrated pathological accumulation of mitochondria in cytochrome c oxidase negative fibers. In situ hybridization demonstrated only deleted mtDNA in cytochrome c oxidase negative fibres. We conclude that occurrence of deleted mtDNA correlates with phenotypic expression and that the duplicated mtDNA might serve as a generator of deletions, but is not directly pathogenic.
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg University, S-413 45 Göteborg, Sweden.
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Ann
authors.initials: A
authors.lastname: Gardner
authors.forename: Tore
authors.initials: T
authors.lastname: Hällström
authors.forename: Kristina
authors.initials: K
authors.lastname: Müntzing
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holme
mesh_terms: D015139:Blotting, Southern / Q000379:methods; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics; D045303:Cytochromes b / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000150:complications; D048909:Diabetes Complications; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D034381:Hearing Loss / Q000150:complications; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004272:DNA, Mitochondrial; D045303:Cytochromes b; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV