Genetic Variants of β-Thalassemia and Hemoglobin E β-Thalassemia: A Mutation Profiling Study in the Bangladeshi Population

Background: β-Thalassemia and Hb E β-Thalassemia are among the most prevalent genetic disorders in Bangladesh. Haemoglobin E is also one of the most common hemoglobinopathies worldwide, particularly among individuals of Southeast Asian, Northeast Indian, Sri Lankan, and Bangladeshi descent. It is caused by mutations in the beta-globin gene, leading to various clinical forms such as thalassemia minor, intermediate, major, and other hemoglobinopathies. Objective: The aim of this study was to identify and characterize the spectrum of genetic mutations responsible for β-thalassemia and hemoglobinopathy in the Bangladeshi population, with the goal of improving diagnostic accuracy, supporting carrier screening programs, and informing strategies for genetic counselling and disease prevention. Patients and methods: A total of 100 subjects were included in this study. Among them, 47% (n = 47) were β-thalassemia carriers, 22% (n = 22) were β-thalassemia major patients and 31% (n=31) were Hb E β-Thalassemia patients. The β-thalassemia and hemoglobinopathy phenotype was characterised by measuring RBC indices using a cell counter, reviewing peripheral blood picture under microscope, and measuring fractions of haemoglobin by HPLC method (Variant II). Mutation analysis was performed using the amplification refractory mutation system (ARMS) and DNA sequencing. Results: In this study, a total of 12 pathogenic mutations were identified. Among these, the most prevalent was IVS 1-5 (G>C), accounting for 44% (n = 68), followed by codon 26 (G>A) at 20.26% (n =31), Fr 41–42 (−TTCT) at 11.11% (n = 17), Fr 8–9 (+G) at 6.5% (n = 10), codon 30 (G>C) at 5.23% (n = 8), codon 16 (−C) at 3.92% (n = 6), codon 30 (G>A) at 3.27% (n = 5), IVS 1-130 (G>C) at 1.96% (n = 3), codon 15 (G>A) at 1.30% (n = 2), −90 (C>T) at 0.65% (n = 1), , IVS 1-130 (G>A) at 0.65% (n = 1), and codon 15 (−T) at 0.65% (n = 1). Conclusion: This study will help to understand the inheritance pattern of pathogenic mutations among β-thalassemia and hemoglobinopathy patients and carriers in the Bangladeshi population.