Weinberg R S, Antonarakis S E, Kazazian H H, Dover G J, Orkin S H, Lenes A L, Schofield J M, Alter B P
Blood. 1984 Jun;63(6):1278-84.
To determine whether hemoglobin regulation is normal in diseases affecting beta-globin gene expression, globin synthesis was examined in members of a family of a patient with hereditary persistence of fetal hemoglobin/beta o-thalassemia (HPFH/beta o-thal). The HPFH defect is the Ghanian type II, with a deletion from psi beta 1 to at least 20 kb 3' to beta. The beta o-thal gene has the haplotype II restriction enzyme pattern and has the beta 39 nonsense mutation. Erythroid colonies from blood BFU-E were radiolabeled, and globin chains were separated by gel electrophoresis. Colonies from the beta o-thal heterozygote had non-alpha/alpha ratios more balanced than in the reticulocytes. Gamma synthesis was 11% of non-alpha, which is higher than in reticulocytes, but within the range seen in normal adult colonies. Both HPFH heterozygotes produced 20%-30% gamma in erythroid colonies as well as reticulocytes, although non-alpha/alpha was more balanced in the colonies. The HPFH/beta o-thal patient produced 100% gamma in reticulocytes and in colonies. G gamma and gamma-synthetic proportions were not correlated at the individual colony level in the heterozygotes, suggesting that they had "adult" and not "fetal" progenitor cells. The Hb expression of these adult progenitors is presumably modulated normally in vivo in beta o-thal, but the normal decrease in HbF production does not occur in gene deletion HPFH.
为了确定在影响β珠蛋白基因表达的疾病中血红蛋白调节是否正常，对一名患有胎儿血红蛋白遗传性持续存在/β⁰地中海贫血（HPFH/β⁰地贫）患者家族成员的珠蛋白合成进行了检测。HPFH缺陷为加纳II型，从ψβ1缺失至β基因下游至少20 kb处。β⁰地贫基因具有单倍型II限制性内切酶图谱，并具有β39无义突变。对血液中BFU-E的红系集落进行放射性标记，通过凝胶电泳分离珠蛋白链。β⁰地贫杂合子的集落中非α/α比值比网织红细胞中的更平衡。γ珠蛋白合成占非α珠蛋白的11%，高于网织红细胞中的水平，但在正常成人集落的范围内。两名HPFH杂合子在红系集落和网织红细胞中均产生20%-30%的γ珠蛋白，尽管集落中的非α/α比值更平衡。HPFH/β⁰地贫患者在网织红细胞和集落中均产生100%的γ珠蛋白。在杂合子个体集落水平上，Gγ和γ珠蛋白合成比例不相关，表明它们具有“成人”而非“胎儿”祖细胞。这些成人祖细胞的血红蛋白表达在体内β⁰地贫中可能受到正常调节，但在基因缺失型HPFH中不会出现胎儿血红蛋白产生的正常减少。
