调控基因KLF1变异在遗传性血液病中的研究进展

KLF1是调节红细胞生成以及成人β-珠蛋白基因的表达的关键调控基因。参与激活、调节多个血型抗原表达、珠蛋白基因表达和转换、细胞周期、酶代谢、结构蛋白、血红素合成等相关基因及转录因子,并与这些转录因子在红系调控网络中协同工作,共同参与红系的基因表达。在高通量测序广泛应用以前,KLF1变异一直被认为是及其罕见的。事实上在许多独立的红细胞疾病中都发现了KLF1的突变。这些患者表型因突变类型的不同而各有差异。同时KLF1突变的流行区域也与血红蛋白疾病有一定的重叠。本文将从KLF1结构、功能、突变类型、表型、流行趋势等多个方面探讨其在红细胞疾病中的作用。为关键细胞主要调控因子的变异在一些迄今为止无法解释的遗传疾病中的作用提供一个范例。

Progress in the study of KLF1 mutations in hereditary red blood cell disorders

KLF1 is essential for erythropoiesis and activation of adult b-globin expression.It activates genes that associate with red cell antigen,switching factors,globin synthesis ion heme,structural proteins,metabolic enzymes and cell cycle regulators.KLF1 also modulates expression of other transcription factors that work together in regulatory networks to control gene expression in erythroid cells.Until recently,KLF1 variants were considered to be extremely rare causes of red cell disorders.In fact,it have discovered that a broad range of hitherto unrelated human red cell disorders are caused by variants in KLF1.The phenotype of these patients varies according to the type of mutation.In Southern China,the incidence of KLF1 variants correlates with the distribution of hemoglobinopathies in these regions.Here,we use KLF1 as an example to discuss its role in erythrocyte disease and how variants affecting other master regulators of key cell types will account for conditions with hitherto unexplained genetics.