A heteroplasmic point mutation of mitochondrial tRNALeu(CUN) in non-lymphoid haemopoietic cell lineages from a patient with acquired idiopathic sideroblastic anaemia

Br J Haematol. 1996 Jun;93(4):845-55. doi: 10.1046/j.1365-2141.1996.d01-1724.x.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia, Sideroblastic / genetics*
  • Base Sequence
  • Humans
  • Male
  • Molecular Sequence Data
  • Myelodysplastic Syndromes / genetics*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • RNA / genetics*
  • RNA, Mitochondrial
  • RNA, Transfer, Leu / genetics


  • RNA, Mitochondrial
  • RNA, Transfer, Leu
  • RNA