Table_1_Emerging bone marrow failure syndromes- new pieces to an unsolved puzzle.xlsx

Inherited bone marrow failure (BMF) syndromes are genetically diverse — more than 100 genes have been associated with those syndromes and the list is rapidly expanding. Risk assessment and genetic counseling of patients with recently discovered BMF syndromes is inherently difficult as disease mechanisms, penetrance, genotype-phenotype associations, phenotypic heterogeneity, risk of hematologic malignancies and clonal markers of disease progression are unknown or unclear. This review aims to shed light on recently described BMF syndromes with sparse concise data and with an emphasis on those associated with germline variants in ADH5/ALDH2, DNAJC21, ERCC6L2 and MECOM. This will provide important data that may help to individualize and improve care for these patients.

遗传性骨髓衰竭综合征（Inherited bone marrow failure, BMF）具有高度的遗传异质性——目前已有超过100个基因被证实与这类综合征相关，且相关致病基因的名录仍在快速扩充。对于新近发现的BMF综合征患者，其风险评估与遗传咨询本就颇具挑战，这是因为疾病的发病机制、外显率、基因型-表型关联、表型异质性、血液系统恶性肿瘤患病风险以及疾病进展的克隆标志物等核心信息均尚未明确或未被阐明。本综述旨在对现有数据稀少且描述简洁的新近报道的BMF综合征进行梳理阐释，并重点聚焦于与ADH5/ALDH2、DNAJC21、ERCC6L2及MECOM基因种系变异相关的亚型。本综述将提供关键参考数据，助力实现此类患者的个体化诊疗并优化其临床照护。