Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and increased risk of malignant disease. Next generation sequencing methods have greatly facilitated the discovery of genetic etiology in IBMFS. Recently, de novo mutations activating TP53 were detected in patients with BMFS, mimicking Diamond-Blackfan anemia (DBA), using whole exome sequencing, and these patients were recognized as having a novel disorder. This discovery provides important insights into the previously postulated connection between p53 activation and IBMFS. Furthermore, a novel IBMFS, aldehyde degradation deficiency syndrome, was found in patients with aplastic anemia resembling Fanconi anemia (FA). This disorder is caused by combined inactivating mutations in ADH5 and ALDH2 coding formaldehyde-detoxifying enzymes. In this review, we highlight recent studies on DBA, FA, and their related diseases in Japan.
Keywords: Diamond-Blackfan anemia; Fanconi anemia; Formaldehyde; TP53.