KLF转录因子1(KLF1)和GATA结合蛋白1(GATA1)是启动和调节参与红细胞生成的基因转录的转录因子(TF)。这些TFs具有识别基因中特定核苷酸序列的DNA结合域,它们结合并调节转录。编码KLF1或GATA1的基因变异可导致一系列血液学表型-从良性到严重形式的血小板减少症和贫血;它们还可削弱血型抗原的表达。路德教(LU)血型系统易受TF基因变异,特别是KLF1变体。KLF1基因变体的杂合子个体显示红细胞上的路德教会抗原减少,这通常不能通过常规血凝方法检测到。这种降低的抗原表达被称为In(Lu)表型。为了准确的血型,区分In(Lu)表型很重要,抗原表达非常弱,和真正的Lunull表型,没有抗原表达。国际输血学会血型等位基因数据库记录了与改良的路德教表达相关的KLF1和GATA1变体。这里,我们回顾了KLF1和最近通过调查血型表型和基因型差异定义的新基因变异,对于一份报告,调查原因不明的慢性贫血病例。此外,我们包括对GATA1TF的回顾,包括描述与血清学Lu(a-b-)表型相关的第二个GATA1变异的病例报告。最后,我们回顾了过去和最近关于血型基因DNA序列基序变异的报道,这些变异破坏了GATA1TF的结合,并消除或减少了红系抗原的表达.这篇综述强调了转录过程本身的多样性和复杂性,以及需要考虑这些因素作为准确血型表型鉴定的附加组成部分。
KLF transcription factor 1 (KLF1) and GATA binding protein 1 (GATA1) are transcription factors (TFs) that initiate and regulate transcription of the genes involved in erythropoiesis. These TFs possess DNA-binding domains that recognize specific nucleotide sequences in genes, to which they bind and regulate transcription. Variants in the genes that encode either KLF1 or GATA1 can result in a range of hematologic phenotypes-from benign to severe forms of thrombocytopenia and anemia; they can also weaken the expression of blood group antigens. The Lutheran (LU) blood group system is susceptible to TF gene variations, particularly KLF1 variants. Individuals heterozygous for KLF1 gene variants show reduced Lutheran antigens on red blood cells that are not usually detected by routine hemagglutination methods. This reduced antigen expression is referred to as the In(Lu) phenotype. For accurate blood typing, it is important to distinguish between the In(Lu) phenotype, which has very weak antigen expression, and the true Lunull phenotype, which has no antigen expression. The International Society of Blood Transfusion blood group allele database registers KLF1 and GATA1 variants associated with modified Lutheran expression. Here, we
review KLF1 and recent novel gene variants defined through investigating blood group phenotype and genotype discrepancies or, for one report, investigating cases with unexplained chronic anemia. In addition, we include a
review of the GATA1 TF, including a case report describing the second GATA1 variant associated with a serologic Lu(a-b-) phenotype. Finally, we
review both past and recent reports on variations in the DNA sequence motifs on the blood group genes that disrupt the binding of the GATA1 TF and either remove or reduce erythroid antigen expression. This
review highlights the diversity and complexity of the transcription process itself and the need to consider these factors as an added component for accurate blood group phenotyping.