Huisman T H, Gravely M E, Henson J, Felice A, Wilson J B, Abraham E C, Vella F, Little M W
J Lab Clin Med. 1978 Aug;92(2):311-20.
Two unrelated families are reported in which beta-thalassemia trait occurred with a heterozygosity of Hb G-Philadelphia (alpha2 68(E17)Asn leads to Lys beta2) in one family and with Hb Rampa (alpha2 95(G2)Pro leads to Ser beta2) in the other. The percentage of Hb G-Philadelphia was not influenced by the simultaneous presence of a beta-thalassemai determinant, but that of Hb Rampa was descreased from 20% in the simple heterozygote to about 6% in persons with the Hb Rampa-beta-thalassemia combination. Data from in vitro recombination experiments with isolated alpha X, alpha A, and beta A chains, with heme attached, indicated a preferential formation of Hb A over Hb Rampa but not over Hb G-Philadelphia in conditions of relative beta-chain deficiency. This suggests that the rate of assembly of monomers to form dimers or tetramers can be an important mechanism of controlling the quantity of certain hemoglobin variants with critical substitutions in heterozygotes.
报道了两个不相关的家庭，其中一个家庭中β地中海贫血特征与Hb G-费城（α2 68（E17）天冬酰胺突变为赖氨酸β2）杂合，另一个家庭中与Hb 兰帕（α2 95（G2）脯氨酸突变为丝氨酸β2）杂合。Hb G-费城的百分比不受β地中海贫血决定簇同时存在的影响，但Hb 兰帕的百分比从单纯杂合子中的20%降至Hb 兰帕-β地中海贫血组合个体中的约6%。来自分离的αX、αA和βA链与附着血红素的体外重组实验数据表明，在相对β链缺乏的情况下，优先形成Hb A而非Hb 兰帕，但不优先于Hb G-费城。这表明单体组装形成二聚体或四聚体的速率可能是控制杂合子中具有关键替代的某些血红蛋白变体数量的重要机制。
