title: Evaluation of gastrointestinal mtDNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease characterized by severe gastro-intestinal (GI) dysmotility caused by mutations in the thymidine phosphorylase gene. Thymidine phosphorylase (TP) is involved in the control of the pyrimidine nucleoside pool of the cell. Reduced TP activity induces nucleotide pool imbalances that in turn affect both the rate and fidelity of mtDNA replication, leading to multiple deletions and depletion of mtDNA. By using laser capture microdissection and quantitative real-time-polymerase chain reaction technique, we showed that depletion of mitochondrial DNA (mtDNA) is the most prominent molecular defect in the gut wall of MNGIE patients. Depletion affects severely the smooth muscle cells of muscularis propria and the skeletal muscle component of the upper esophagus, while ganglion cells of the myenteric plexus show only a milder mtDNA reduction.
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome, Italy. carla.giordano@uniroma1.it
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
authors.forename: Giulia
authors.initials: G
authors.lastname: d'Amati
mesh_terms: D004272:DNA, Mitochondrial / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology*; D018628:Gene Dosage; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000378:metabolism / Q000473:pathology*; D007834:Lasers; D042282:Microdissection / Q000379:methods; D017237:Mitochondrial Encephalomyopathies / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D039141:Muscular Dystrophy, Oculopharyngeal; D009886:Ophthalmoplegia / Q000151:congenital; D016133:Polymerase Chain Reaction / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D013385:Succinate Dehydrogenase / Q000378:metabolism; D028361:Mitochondrial Diseases
chemical_list: D004272:DNA, Mitochondrial; D011451:Prostaglandin-Endoperoxide Synthases; D013385:Succinate Dehydrogenase