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A heteroplasmic point mutation of mitochondrial tRNA Leu(CUN) in non‐lymphoid haemopoietic cell lineages from a patient with acquired idiopathic sideroblastic anaemia
Author(s) -
Gattermann Norbert,
Retzlaff Stefan,
Wang YanLing,
Berneburg Mark,
H einisch Jürgen,
Wlaschek Meinhard,
Aul Carlo,
Schneider Wolfgang
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1724.x
Subject(s) - heteroplasmy , point mutation , biology , mitochondrial dna , mutation , microbiology and biotechnology , sideroblastic anemia , transfer rna , melas syndrome , mitochondrial disease , mitochondrion , genetics , mitochondrial myopathy , gene , rna
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 defect leading to impaired reduction of ferric iron (Fe 3 + ) to ferrous iron (Fe 2 + ), 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.