title: Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency.
abstract: A 12-year-old patient with mitochondrial DNA (mtDNA) depletion syndrome due to TK2 gene mutations has been evaluated serially over the last 10 years. We observed progressive muscle atrophy with selective loss of type 2 muscle fibers and, despite severe depletion of mtDNA, normal activities of respiratory chain (RC) complexes and levels of COX II mitochondrial protein in the remaining muscle fibers. These results indicate that compensatory mechanisms account for the slow progression of the disease. Identification of factors that ameliorate mtDNA depletion may reveal new therapeutic targets for these devastating disorders.
authors.affiliation: Centre d'Investigacions en Bioquímica i Biología Molecular, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Maya R
authors.initials: MR
authors.lastname: Vilà
authors.forename: Joan
authors.initials: J
authors.lastname: Villarroya
authors.forename: Elena
authors.initials: E
authors.lastname: García-Arumí
authors.forename: Amparo
authors.initials: A
authors.lastname: Castellote
authors.forename: Anna
authors.initials: A
authors.lastname: Meseguer
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Manuel
authors.initials: M
authors.lastname: Roig
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D004579:Electron Transport / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D013937:Thymidine Kinase / Q000172:deficiency* / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers; C105339:thymidine kinase 2; D013937:Thymidine Kinase