Identification of the exact position of variant in HBA1, HBA2 or its patchworks is mandatory to support the therapeutic aims in β-thalassemia major, by identifying specific modulators for the reactivation of fetal hemoglobin production.
β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates.
Two common underlying mechanisms include co-inheritance of alpha globin gene deletions in homozygous thalassemia intermedia and presence of XmnI polymorphism.
All patients, who were on the standard treatment protocol, were subsequently divided into two groups according to their genotype, group A (92): TM with no mitigating factor and group B (34): TM carrying one or more mitigating factors in the beta- and/or alpha-globin genes.
Comparison of the beta-globin gene cluster haplotypes, alpha globin genotypes and beta gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co-inheritance of a high Hb F determinant associated with the - + - + + 5' beta haplotype and the inheritance of a mild beta-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians.