[Diagnostic targets and exosome sequence analysis of Diamond-Blackfan anemia in Japan]

Diamond-Blackfan anemia (DBA) is a rare, inherited, congenital bone marrow failure syndrome, which typically manifests in infancy. In addition, the disease is often accompanied by normochromic macrocytic anemia and acute reticulocytopenia in the peripheral blood and by selective deficiency of erythroid precursors in the normocellular bone marrow. Approximately 50% of patients with DBA exhibit growth retardation and multiple congenital anomalies, which primarily include craniofacial dysmorphism, upper-limb abnormalities, urogenital malformations, and congenital heart defects. In addition, heterozygous mutations in genes encoding ribosomal proteins (RP) that lead to a loss of function of the genes are detected in nearly 60% of patients with DBA. As a majority of identified causative genes belong to RP genes, the impairment of ribosome biogenesis is considered accountable for the disease. This study aims to outline the molecular pathology of DBA and the causative gene RPS15A isolated using our exosome analysis.