Camaschella C, Serra A, Gottardi E, Alfarano A, Revello D, Mazza U, Saglio G
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
Blood. 1990 Feb 15;75(4):1000-5.
A new deletion of the beta-globin gene cluster has been characterized in two Italian brothers who are heterozygous carriers of a G gamma A gamma hereditary persistence of fetal hemoglobin (HPFH). Restriction endonuclease mapping and DNA sequencing of the region encompassing the breakpoint show that the deletion starts 3.2 kilobases (kb) upstream from the delta gene and ends within the enhancer region 3' to the beta-globin gene. Here the deletion removes one of the four binding sites for an erythroid specific transcriptional factor (NF-E1). The molecular comparison of the new deletion with others of similar size and location but associated with a delta beta-thalassemia phenotype suggests that the residual enhancer element, relocated near gamma genes, may increase the fetal hemoglobin (HbF) expression above the level observed in delta beta-thalassemia.
在两名意大利兄弟中鉴定出一种新的β-珠蛋白基因簇缺失，他们是胎儿血红蛋白遗传性持续存在（HPFH）的GγAγ杂合携带者。对包含断点区域的限制性内切酶图谱分析和DNA测序表明，该缺失始于δ基因上游3.2千碱基（kb）处，并在β-珠蛋白基因3'端的增强子区域内终止。此处的缺失移除了一种红系特异性转录因子（NF-E1）的四个结合位点之一。将这种新缺失与其他大小和位置相似但与δβ地中海贫血表型相关的缺失进行分子比较，结果表明，重新定位到γ基因附近的残余增强子元件可能会使胎儿血红蛋白（HbF）的表达增加，高于在δβ地中海贫血中观察到的水平。
