Ito Etsuro, Toki Tsutomu, Kamio Takuya, Terui Kiminori
Department of Pediatrics, Hirosaki University Graduate School of Medicine.
Department of Community Medicine, Hirosaki University Graduate School of Medicine.
Rinsho Ketsueki. 2021;62(10):1455-1464. doi: 10.11406/rinketsu.62.1455.
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.
遗传性骨髓衰竭综合征（IBMFS）是一组异质性的遗传疾病，其特征为骨髓衰竭、先天性异常以及患恶性疾病的风险增加。新一代测序方法极大地促进了IBMFS遗传病因的发现。最近，通过全外显子组测序在患有骨髓衰竭综合征（BMFS）、酷似先天性纯红细胞再生障碍性贫血（DBA）的患者中检测到激活TP53的新发突变，这些患者被认定患有一种新型疾病。这一发现为先前推测的p53激活与IBMFS之间的联系提供了重要见解。此外，在酷似范可尼贫血（FA）的再生障碍性贫血患者中发现了一种新型IBMFS，即醛降解缺陷综合征。这种疾病是由编码甲醛解毒酶的ADH5和ALDH2的复合失活突变引起的。在这篇综述中，我们重点介绍了日本最近关于DBA、FA及其相关疾病的研究。
