PDF(Pubmed)
Abstract：
The MECOM gene encodes multiple protein isoforms that are essential for hematopoietic stem cell self-renewal and maintenance. Germline MECOM variants have been associated with congenital thrombocytopenia, radioulnar synostosis and bone marrow failure; however, the phenotypic spectrum of MECOM-associated syndromes continues to expand and novel pathogenic variants continue to be identified. We describe eight unrelated patients who add to the previously known phenotypes and genetic defects of MECOM-associated syndromes. As each subject presented with unique MECOM variants, the series failed to demonstrate clear genotype-to-phenotype correlation but may suggest a role for additional modifiers that affect gene expression and subsequent phenotype. Recognition of the expanded hematologic and non-hematologic clinical features allows for rapid molecular diagnosis, early identification of life-threatening complications, and improved genetic counseling for families. A centralized international publicly accessible database to share annotated MECOM variants would advance their clinical interpretation and provide a foundation to perform functional MECOM studies.
摘要：
MECOM基因编码造血干细胞自我更新和维持所必需的多种蛋白质同种型。种系MECOM变异与先天性血小板减少症有关，尺桡骨融合和骨髓衰竭；然而，MECOM相关综合征的表型谱不断扩大,新的致病变异体也在不断被发现.我们描述了八名无关患者，他们增加了MECOM相关综合征的先前已知表型和遗传缺陷。由于每个受试者都有独特的MECOM变体，该系列未能证明基因型与表型之间有明确的相关性,但可能提示了影响基因表达和随后表型的其他修饰因子的作用.对扩大的血液学和非血液学临床特征的识别允许快速的分子诊断。早期发现危及生命的并发症，和改善家庭遗传咨询。一个中央的国际公开可访问的数据库，以共享带注释的MECOM变体将促进其临床解释，并为执行功能性MECOM研究提供基础。
