Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene
Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene
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DOI：
10.1182/blood.v90.2.822.822_822_830
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发表时间：
1997-07-15
期刊：
影响因子：
20.3
通讯作者：
Yamamoto, M
中科院分区：
文献类型：
--
作者：
Furuyama, K;Fujita, H;Yamamoto, M
为了阐明pyridoxin -refractory X-linked sideroblastic anemia （XLSA）是如何发生的，我们分析了该贫血患者的红细胞特异性5-氨基乙酰酸合成酶（ALAS-E）基因，发现该酶在患者骨髓细胞中的活性和数量约为正常对照的5%。在鹌鹑成纤维细胞的瞬时转染分析中，发现线粒体中积累了比成熟的ALAS-E更大的异常加工蛋白。结合ala - e前体的体外转录/翻译和前体导入离体小鼠线粒体的实验，可重复检测到这些蛋白。这些结果表明，引起pyridoine -refractory XLSA的突变影响了ALAS-E前体的加工，从而引起了ALAS-E蛋白的不稳定性。(C) 1997年由美国血液病学会出版。
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. (C) 1997 by The American Society of Hematology.