Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene

Kazumichi Furuyama, Hiroyoshi Fujita, Tadashi Nagai, Kentaro Yomogida, Hiroshi Munakata, Masao Kondo, Akiro Kimura, Atsushi Kuramoto, Norio Hayashi, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

To elucidate how pyridoxine-refractory X-linked sideroblastic anemia (XLSA) develops, we analyzed the erythroid-specific 5-aminolevulinate synthase (ALAS-E) gene of a patient with the anemia. The activity and amount of the enzyme in bone marrow cells of the patient were found to be approximately 5% of the normal control. We identified a point mutation, which introduces an amino acid substitution from Asp 190 to Val. In transient transfection analyses using quail fibroblasts, accumulation of aberrantly processed proteins, the sizes of which were larger than that of mature ALAS- E, was found in mitochondria. The proteins were reproducibly detected in assays combining in vitro transcription/translation of ALAS-E precursor and import of the precursor into isolated mouse mitochondria. These results suggest that the mutation causing pyridoxine-refractory XLSA affects the processing of the ALAS-E precursor, thus provoking instability of the ALAS-E protein.

Original languageEnglish
Pages (from-to)822-830
Number of pages9
JournalBlood
Volume90
Issue number2
DOIs
Publication statusPublished - 1997 Jul 15
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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