Hb P-Nilotic in association with βo-thalassemia : cis-mutation of a hemoglobin βa chain regulatory determinant?

Abstract

Hb P-Nilotic which is produced by a hybrid of β and δ genes was found in several members of a Sudanese family, three of whom had an associated β-thalassemia. Chemical analyses confirmed the crossover between positions 22 and 50 of the βδP chain. The Hb P-Nilotic heterozygote had completely normal hematology, but the patients with the Hb P-Nilotic-β-thalassemia condition had moderately severe clinical and hematological abnormalities which were considerably more pronounced than those in the father who had a β-thalassemia heterozygosity. The absolute cellular contents of normal and abnormal non-α chains in these subjects and the results of in vitro chain synthesis analyses suggested that the thalassemia gene in this family is of the βo type and that the βA gene which is present in cis to the βδP gene is incapable of being stimulated when the βo-thalassemia determinant is present in trans. It is proposed that a number of recombination events produced a βδP hybrid gene with duplication of the βA gene in cis as well as a change in an untranscribed strand of DNA which controls the expression of the βA gene.