Spectrum of Beta Globin Gene Mutations in Egyptian Children with beta-Thalassemia

Background: The molecular defects resulting in a beta-thalassemia phenotype, in the Egyptian population, show a clear heterogenic mutations pattern. PCR-based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of beta-thalassemia is necessary for carrier screening, genetic counseling, and to offer prenatal diagnosis. The aim of the work: was to evaluate the different beta-globin gene mutations in two hundred beta-thalassemic Egyptian children. Subjects and Methods: This study was carried out on two hundred beta-thalassemic Egyptian children covering most Egyptian Governorates including 158 (79%) children with thalassemia major (TM) and 42 (21%) children with thalassemia intermedia(TI). All patients were subjected to meticulous history taking, clinical examination, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of the beta-globin gene to detect the frequency of different mutations. Results: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6( T>C) 40%, IVS I-1(G>A) 24%, IVS I-5(G>C) 10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon"Cd"39(C>T) 4%, -87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G>C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was a considerable variation in phenotypic severity among patients resulting from the interaction of different beta degrees and beta+mutations. Furthermore, no genotype-phenotype association was found both among the cases with thalassemia major and the cases with thalassemia intermedia. Conclusion: Direct DNA sequencing provides insights for the frequency of different mutations in patients with beta-thalassemia including rare and/or unknown ones. The most common mutations in Egyptian children with beta thalassemia were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A) 24%, IVS I-5(G>C) 10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%.