title: A heteroplasmic point mutation of mitochondrial tRNALeu(CUN) in non-lymphoid haemopoietic cell lineages from a patient with acquired idiopathic sideroblastic anaemia.
abstract: Acquired idiopathic sideroblastic anaemia (AISA) has been proposed to be a disorder of mitochondrial DNA (mtDNA). The hallmark of mitochondrial iron overload may be attributable to a respiratory chain defeat leading to impaired reduction of ferric iron (Fe3+) to ferrous iron (Fe2+), which is essential to the last step of mitochondrial haem biosynthesis. In a 71-year-old patient we identified a point mutation in one of the two mitochondrial transfer-RNAs coding for leucine (tRNA(leu)(CUN)). The mutation involves a G --> A transition in the anticodon loop, immediately adjacent to the anticodon triplet (mtDNA position 12301). The mutated guanine is highly conserved in a wide range of species. The mutation is heteroplasmic, i.e. there is a mixture of normal and mutated mitochondrial genomes (ratio c. 50:50). Heteroplasmy of mtDNA is not found in normal individuals, but is a typical feature of mitochondrial cytopathies. The point mutation was present in the patient's bone marrow and whole blood samples, in purified platelets, and in the granulocyte/erythrocyte pellet after mononuclear cell separation by density gradient centrifugation. The mutation was not found in T- and B-lymphocytes isolated by immunomagnetic bead separation. It was also absent from buccal mucosa cells and cultured skin fibroblasts. This pattern of involvement suggests that the mutation occurred in a self-renewing myeloid stem cell of the CFU-GEMM type.
authors.affiliation: Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gattermann
authors.forename: S
authors.initials: S
authors.lastname: Retzlaff
authors.forename: Y L
authors.initials: YL
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Berneburg
authors.forename: J
authors.initials: J
authors.lastname: Heinisch
authors.forename: M
authors.initials: M
authors.lastname: Wlaschek
authors.forename: C
authors.initials: C
authors.lastname: Aul
authors.forename: W
authors.initials: W
authors.lastname: Schneider
mesh_terms: D000368:Aged; D000756:Anemia, Sideroblastic / Q000235:genetics*; D001483:Base Sequence; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000235:genetics
chemical_list: D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D012313:RNA