title: Phenotypic expression of mitochondrial genotypes in cultured skin fibroblasts and in Epstein-Barr virus-transformed lymphocytes in Pearson syndrome.
abstract: Pearson syndrome is a fatal disorder involving the hematopoietic system and exocrine pancreas. Mitochondrial respiratory chain deficiencies and/or rearrangements of the mitochondrial DNA were consistently observed in all patients. We report here on the variant phenotypic expression of mitochondrial genotypes in cultured cells from a patient with Pearson syndrome. Skin fibroblasts and lymphocytes harbored, respectively, 60% and 80% of deleted mtDNA molecules initially and displayed defective respiratory chain activities. In both cases, there was a progressive recovery of respiratory chain activities during in vitro cell proliferation due to the loss of deleted mtDNA molecules in cultured skin fibroblasts and to an increase in the mtRNA translation efficiency in Epstein-Barr virus-transformed lymphocytes. The present study suggests that various cellular responses to abnormal mitochondrial genotypes might contribute to the tissue-specific expression of mitochondrial disorders in vivo.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital des Enfants Malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: T
authors.initials: T
authors.lastname: Bourgeron
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D000756:Anemia, Sideroblastic / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005347:Fibroblasts; D004854:Herpesvirus 4, Human; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010182:Pancreatic Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D010641:Phenotype; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D012313:RNA; D003576:Electron Transport Complex IV