Molecular pathogenesis in Diamond–Blackfan anemia

Diamond–Blackfan anemia (DBA) is a congenital anemia and a broad spectrum of developmental abnormalities that presents soon after birth. The anemia is due to a failure of erythropoiesis with normal platelet and myeloid lineages. Approximately 10–20% of DBA cases are inherited. Genetic studies have identified heterozygous mutations in at least one of eight ribosomal protein genes in up to 50% of cases. Mutations in RPL5 and RPL11 are at a high risk for developing malformation. Especially, mutations in RPL5 are associated with multiple physical abnormalities, including cleft lip/plate and thumb and heart anomalies. Recently, the 5q− syndrome, a subtype of myelodysplastic syndrome characterized by a defect in erythroid differentiation, is caused by a somatically acquired deletion of chromosome 5q, which results in haploinsufficiency of RPS14. These data indicate that abnormalities in ribosome function are broadly implicated in both congenital and acquired bone marrow failure syndrome in humans.