Hb S(C)-beta+-thalassaemia: different mutations are associated with different levels of normal Hb A

Abstract

Analysis of amplified DNA through hybridization with 32P-labelled synthetic oligonucleotide probes has provided data about the molecular abnormality for beta-thalassaemic globin genes present in 32 Black and eight Mediterranean patients with Hb S(C)-beta+-thalassaemia. The patients were categorized according to these beta-thalassaemia mutations, and average haematological and haemoglobin composition data were compared for each of four different groups. Twenty-eight Black patients had the -29 A----G substitution and four had the -88 C----T substitution; all had mild disease with comparable haematology and an average Hb A level of 20%. Six Mediterranean patients had the IVS-1, 110 G----A mutation; their haematological data were nearly the same as that for the Black patients except for a lower Hb A value of 11%. Two Turkish patients with the IVS-2, 745 C----G mutation were more severely affected with mild sickling disease and low Hb A levels of 5%. Hb F levels varied greatly because of age differences; high G gamma values were observed only in patients with a beta-thalassaemia chromosome having an Xmn I site 5' to G gamma. The data readily explain the variability in Hb A level that has been repeatedly noted in patients with Hb S(C)-beta+-thalassaemia.