Beta Thalassemia is the most common single gene disorder in the world. It is caused by mutations in the beta globin gene. In India 6-8 mutations in the beta globin gene account for majority of the cases. Common mutations are screened using ARMS/RDB/GAP-PCR and the other mutations by Sanger sequencing. Carriers of beta thalassemia can be identified by quantitating HbF/HbA2/Other Hb Variants by HPLC or electrophoresis
Beta thalassemia is an autosomal recessive genetic disorder that results in reduction of beta-globin chains that are essential to form hemoglobin; the protein required to transport oxygen to tissues. The disease presents in childhood as a transfusion-dependent anaemia (Thalassaemia major). On the other hand, thalassaemia minor, or thalassaemia trait, occurs when the person carries a single copy of the defective gene.
Most commonly, missense or splice-site variants are observed in the beta-globin gene (HBB); but variants in the promoter, poly-A tail and deletions are also identified. Several haemoglobinopathies also occur due to genetic alterations in HBB; the most common being HbS (sickle cell haemoglobin) and HbE. These can occur in compound heterozygous states with other beta-thalassaemia mutations resulting in clinical symptoms. Molecular testing is used for diagnosis in transfused patients and for prenatal testing. Carrier states in parents of thalassaemia patients can be ascertained by HPLC.
In India, 6-8 mutations in the beta globin gene account for majority of the cases.
Common mutations are screened using ARMS-PCR or reverse dot-blot hybridization (RDB). If negative, Sanger sequencing of HBB followed by 619bp deletion by gap-PCR are carried out.