TY - JOUR
T1 - Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene
AU - Furuyama, Kazumichi
AU - Fujita, Hiroyoshi
AU - Nagai, Tadashi
AU - Yomogida, Kentaro
AU - Munakata, Hiroshi
AU - Kondo, Masao
AU - Kimura, Akiro
AU - Kuramoto, Atsushi
AU - Hayashi, Norio
AU - Yamamoto, Masayuki
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1997/7/15
Y1 - 1997/7/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.v90.2.822
DO - 10.1182/blood.v90.2.822
M3 - Article
C2 - 9226183
AN - SCOPUS:0030752517
VL - 90
SP - 822
EP - 830
JO - Blood
JF - Blood
SN - 0006-4971
IS - 2
ER -