TY - JOUR
T1 - Molecular pathophysiology and genetic mutations in congenital sideroblastic anemia
AU - Fujiwara, Tohru
AU - Harigae, Hideo
N1 - Funding Information:
We thank the member of Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, for their support. This manuscript is supported by JSPS (Japan Society for the Promotion of Science) KAKENHI Grant No. 18K08314 to T.F., and 26293225/17H04668 to H.H.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/3
Y1 - 2019/3
N2 - Sideroblastic anemia is a heterogeneous congenital and acquired disorder characterized by anemia and the presence of ring sideroblasts in the bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes involved in the heme biosynthesis, iron–sulfur [Fe–S] cluster biosynthesis, and mitochondrial protein synthesis. The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. To date, a remarkable number of genetically undefined CSA cases remain, but a recent application of the next-generation sequencing technology has recognized novel causative genes for CSA. However, in most instances, the detailed molecular mechanisms of how defects of each gene result in the abnormal mitochondrial iron accumulation remain unclear. This review aims to cover the current understanding of the molecular pathophysiology of CSA.
AB - Sideroblastic anemia is a heterogeneous congenital and acquired disorder characterized by anemia and the presence of ring sideroblasts in the bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes involved in the heme biosynthesis, iron–sulfur [Fe–S] cluster biosynthesis, and mitochondrial protein synthesis. The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. To date, a remarkable number of genetically undefined CSA cases remain, but a recent application of the next-generation sequencing technology has recognized novel causative genes for CSA. However, in most instances, the detailed molecular mechanisms of how defects of each gene result in the abnormal mitochondrial iron accumulation remain unclear. This review aims to cover the current understanding of the molecular pathophysiology of CSA.
KW - ALAS2
KW - Congenital sideroblastic anemia
KW - Heme
KW - Iron
KW - Mitochondria
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U2 - 10.1016/j.freeradbiomed.2018.08.008
DO - 10.1016/j.freeradbiomed.2018.08.008
M3 - Review article
C2 - 30098397
AN - SCOPUS:85051524741
VL - 133
SP - 179
EP - 185
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -