Characterisation of β-thalassemia mutations in a tertiary care referral hospital in southern India- A descriptive study.

Purpose: Thalassemia is the most prevalent autosomal single-gene disorder. More than 250 mutations that impact β-globin gene expression levels through diverse mechanisms are known to cause β-thalassemia. Regional variations in β-thalassemia mutations are common. This study was undertaken to study the common β-thalassemia mutations in a tertiary care hospital in Puducherry, southern India.

Methods: The study was conducted over two years (2020-2021). Patients with β-thalassemia, their carrier parents and siblings, mainly from Puducherry and various districts of Tamil Nadu, were included to screen prevalent mutations. The genomic DNA isolated from whole blood samples was hybridized using a strip assay kit by reverse dot blot hybridization. For a few samples, DNA sequencing was done from a referral lab.

Results: Among the 92 cases, comprising 40 index cases and 52 family members, IVS I-5(G > C) was the most common mutation detected, accounting for 78%, followed by Cd 15(G > A) at 5.3% of all mutant alleles. Additional β-thalassemia mutations identified included - 28 (A > G) and Poly A site (T > C) through sequencing, along with FS Cd 41/42 (-TCTT) and Cd 8/9 (+ G) detected via strip assay. One index case of Sickle-β thalassemia with IVS I-5(G > C) + Cd 6(A > T) and another case of HbE-β thalassemia with Cd8/9(+ G) + Cd 26(G > A) mutant alleles was also identified. Uncharacterized mutant alleles in the study accounted for 4.5%.

Conclusion: This study helped us to identify the common mutation patterns in our hospital population. Additional mutations could be detected by sequencing beyond those identified through strip assay. Mutation screening plays a crucial role in genetic counselling and prenatal diagnosis.