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

摘要: 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 anemia. The activity and amount enzyme in bone marrow cells were found to be approximately 5% normal control. We identified point mutation, which introduces an amino acid substitution from Asp 190 Val. In transient transfection analyses using quail fibroblasts, accumulation aberrantly processed proteins, sizes larger than that mature ALAS-E, was mitochondria. proteins reproducibly detected assays combining vitro transcription/translation ALAS-E precursor import into isolated mouse These results suggest mutation causing XLSA affects processing precursor, thus provoking instability protein.