The spectrum of β-thalassemia mutations in Gaza Strip, Palestine

Backgroundβ-Thalassemia is a disorder caused by mutations at the hemoglobin β-gene (HBB) locus. Its most important manifestation, the major form, is characterized by severe hypochromic and hemolytic anemia and is inherited in an autosomal recessive mode. In Gaza Strip, Palestine 0.02% of the population has been identified as β-thalassemia major.Design and methodsAn assessment of mutations was performed in 49 transfusion dependent patients with β-thalassemia major and in 176 β-thalassemia carriers diagnosed with a mean erythrocyte cell volume (MCV) < 80 fl and a proportion of HbA2 > 3.5%. In addition 39 individuals suspicious for β-thalassemia carrier status due to a reduced MCV (< 80 fl) but a normal HBA2 were screened.ResultsBy screening with three hybridization assays a proportion of 80% of the thalassemic chromosomes from patients and carriers was identified to carry five different mutations of the hemoglobin (Hb) β-gene. Subsequent DNA sequencing confirmed these and revealed further 9% of the chromosomes to be affected by other mutations. In addition six chromosomes from suspicious carriers were detected to carry β-thalassemia mutations. Of the 15 different HBB mutations identified the variant IVS-I-110 G > A was the most frequent mutation identified in 34% of the thalassemic chromosomes, followed by IVS-I-1 G > A, IVS-I-6 T > C, Codon 39 C > T, and Codon 37 G > A. Three novel HBB variants were discovered by direct sequencing of the gene: 5′ UTR-50 (−/G), 5′ UTR-43 C > T, and IVS-II-26 T > G.ConclusionsThe spectrum of HBB mutations described is of the Mediterranean type whereby the allele frequencies of the most common mutations differ from those, which were previously described for the population of the Gaza Strip and other Palestinian populations. The data presented may promote the introduction of molecular testing to the Palestinian premarital screening program for β-thalassemia in Gaza Strip, which will improve the screening protocol and genetic counseling in the future.