Molecular characterization of beta-thalassemia in Egyptians.

We sought to determine the spectrum of mutations producing beta-thalassemia in Egypt using genomic PCR and a variety of mutation-screening procedures. Thirty-four beta-thalassemia and three Hb S/beta-thalassemia patients originating from different regions of Egypt were studied, and the causative mutation was found in 69 of 71 (97%) beta-thalassemia genes. Four mutations accounted for 78% of beta-thalassemia genes in this population; IVS-1, nt 110 (41%), IVS-1 nt 6 (13%), IVS-1, nt 1 (13%), and IVS-2, nt 848 (11%). The latter allele, a C-A mutation at the third nucleotide of an acceptor site consensus sequence, has been described previously only in one Egyptian, one Iranian, one Tunisian, and one Black American patient. Nine other alleles each accounted for 1-3% of beta-thalassemia genes. Among these was one codon 27 allele (Hb Knossos), two frameshift 106/107 alleles previously seen only in a Black American, and a rarely observed mutation in the distal promoter region of the beta-globin gene, -87 (C-A). Our results suggest that from a molecular genetic standpoint a beta-thalassemia prevention program based on carrier screening and prenatal diagnosis can be implemented in Egypt. In couples at risk for beta-thalassemia, the causative mutation should be identifiable in both members in 92% and in one member in the remaining 8%.