Collins F S, Metherall J E, Yamakawa M, Pan J, Weissman S M, Forget B G
Nature. 1985;313(6000):325-6. doi: 10.1038/313325a0.
Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, alpha 2 gamma 2) in the absence of erythropoietic stress. Several genetic types have been discerned based on the level of HbF produced, the relative contributions of the duplicated fetal (G gamma and A gamma) globin genes, and the presence or absence of deletions involving the beta and delta genes in cis to the mutation. Greek HPFH is a non-deletion variety in which heterozygotes produce 10-20% HbF, predominantly due to overproduction of the A gamma chain. We have cloned a 40-kilobase (kb) region of the beta-globin cluster from a Greek HPFH allele and report here that a point mutation (G----A) occurs 117 base pairs (bp) 5' to the cap site of the A gamma-globin gene, just upstream of the distal CCAAT sequence. The corresponding region of the G gamma-globin gene is normal. We discuss the implications of this finding for the developmental regulation of globin gene expression.
遗传性胎儿血红蛋白持续存在（HPFH）是一种良性病症，其特征为在无红细胞生成应激的情况下，成年期产生超过1%的胎儿血红蛋白（HbF，α2γ2）。根据所产生的HbF水平、重复的胎儿（Gγ和Aγ）珠蛋白基因的相对贡献以及与突变顺式排列的β和δ基因缺失的有无，已识别出几种遗传类型。希腊型HPFH是一种非缺失型，其中杂合子产生10% - 20%的HbF，主要是由于Aγ链的过量产生。我们从一个希腊型HPFH等位基因克隆了β珠蛋白基因簇的一个40千碱基（kb）区域，在此报告一个点突变（G→A）发生在Aγ珠蛋白基因帽位点5'端117个碱基对（bp）处，恰好在远端CCAAT序列的上游。Gγ珠蛋白基因的相应区域是正常的。我们讨论了这一发现对珠蛋白基因表达发育调控的意义。
