MOLECULAR CHARACTERIZATION OF HB S(C) BETA-THALASSEMIA IN AMERICAN BLACKS

An extension of previous reports describing the molecular defects and hematological abnormalities in black patients with Hb S(C) beta-thalassemia living in the Southeastern United States is presented. As many as 58 patients with Hb S-beta+-thalassemia, 16 with Hb C-beta+-thalassemia and 12 with Hb S-beta-degrees-thalassemia have been studied. Patients with Hb S(C) beta+-thalassemia type 2 (high Hb A values) were most common; the thalassemia was due to mutations in the promoter of the beta-globin gene [-88 (C --> T) and -29 (A --> G)] or at the polyadenylation signal (T --> C). Two patients with lower Hb A values (type 1) carried a mutation in the first intron of the beta-globin gene (IVS-I-5: G --> T). The simultaneous presence of an alpha-thalassemia -2(-alpha/) resulted in some modifications of the hematological parameters, but had a minimal effect on the clinical condition. Patients with Hb S-beta-degrees-thalassemia had lower hemoglobin values, lower number of red blood cells, and lower MCHC values and suffered more frequently from complications than the patients with Hb S-beta+-thalassemia. A total of 17 different beta-thalassemia mutations were observed in 128 chromosomes; two mild beta+-thalassemia mutations [-88(C --> T) and -29(A --> G)] account for more than 80% of the thalassemic chromosomes.