Mutational analysis of thalassemia in transfusion-dependent beta-thalassemia patients from central India

Thalassemia and hemoglobin (Hb) disorders are the most common genetic disorders among humans. These disorders entail huge morbidity, economic, and psychological burden on the families of the affected. Genetic counseling and prenatal diagnosis are the steps, which helps to reduce this burden. At present, there is paucity of data on the mutational spectrum of thalassemia from the central Indian region.

Blood samples were collected from 62 transfusion-dependent patients, demographic and relevant data were collected and screened for the two rare mutations - 88 (C-T) and CAP + 1 (A-G) using amplification refractory mutation system-polymerase chain reaction (PCR) and GAP PCR technique. PCR was performed for rare Hb disorders such as Hb Lepore and δ β chain disorder by GAP PCR in addition to five common Indian beta-thalassemia mutations IVS1-5 (G-C), IVS1-1 (G-T), Cd41/42 (-TCTT), Cd8/9 (+G), 619 bp deletion.

Overall 93.5% of the mutations could be identified. Among the abnormal Hb, sickle cell and HbE were found at 4% and 3% of all the loci studied. We also reported two loci with Hb δ β and one locus with Hb Lepore in the present samples. IVS I-5 (G-C) was the common mutation (46%) followed by IVS I-1 (G-T) (12%) and 619 bp (9%).

The identification of the genotypes helps to define the severity of the phenotype, plan therapy and form the basis of the comprehensive diagnostic database that would be useful not only for genetic counseling but prenatal diagnosis as well, contributing to the current focus of the National Policy to prevent and control hemoglobinopathies.