VARIABILITY IN INTERACTION OF BETA-THALASSEMIA WITH ALPHA-CHAIN VARIANTS HB G-PHILADELPHIA AND HB RAMPA

  • 1 January 1978
    • journal article
    • research article
    • Vol. 92  (2) , 311-320
Abstract
Two unrelated families are reported in which a .beta.-thalassemia trait occurred with a heterozygosity for Hb G-Philadelphia (.alpha.2 68(E17)Asn .fwdarw. Lys .beta.2) in 1 family and with Hb Rampa (.alpha.2 95(G2)Pro .fwdarw. Ser.beta.2) in the other. The percentage of Hb G-Philadelphia was not influenced by the simultaneous presence of a .beta.-thalassemia determinant, but that of Hb Rampa was decreased 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. The rate of assembly of monomers to form dimers or tetramers apparently can be an important mechanism of controlling the quantity of certain Hb variants with critical substitutions in heterozygotes.