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

研究成果: Article査読

48 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)822-830
ページ数9
ジャーナルBlood
90
2
DOI
出版ステータスPublished - 1997 7 15
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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