Alpha globin gene deletions in amelioration of clinical severity in beta haemoglobinopathy subjects with the β0/β+ genotype

Abstract

AbstractThalassemia is the commonest inherited hemoglobinopathy worldwide. Variation of clinical symptoms entail differences in disease-onset and transfusion requirements. Our objective was to investigate the role of alpha gene deletions in modulating the clinical heterogeneity of thalassemia syndromes. A total of 214 individuals with diagnosed beta-thalassemia major/intermedia were included in the study. Beta globin mutations were determined and categorized as β+ and β0. Eight common alpha globin gene deletions were detected by multiplex GAP-PCR. Out of the 17 individuals with β+/β+, 16 did not harbour alpha deletions (αα/αα), and most of them were non-severe. On the other hand, out of 46 individuals with β0/β0, 30 did not reveal alpha deletions, whereas 16 possessed one or more alpha deletion(s). Accordingly, most of them presented as clinically severe. Out of the 151 β0/β+ individuals, 119 were negative for alpha deletion, whereas 32 possessed alpha deletions. It was observed that, only in this last category, alpha deletions made a significant contribution (P< 0.0001) in modulation of clinical non severity in this genotype. In conclusion, alpha globin gene deletions play a role to help in ameliorating the phenotype in the β+/β0 genotype. However, they may have only minor/no role in patients with β+/β+ or β0/β0 genotype.