Genotype–Phenotype Correlation of β-Thalassemia in the Indian College Student Population: Insights and Challenges in Screening and Molecular Diagnosis

Introduction

Thalassemia is an autosomal recessive genetic disorder stemming from abnormal haemoglobin levels, a significant global health concern. Individuals carrying one altered allele, known as thalassemia carriers, typically lead normal lives without symptoms, constituting around 4.5% of the world’s population. However, when a child inherits defective globin genes from both parents, thalassemia major manifests, necessitating lifelong reliance on blood transfusions and posing challenges in maintaining an adequate national blood supply. Thalassemia complications include iron overload, cardiovascular issues, and bone deformities. ^2-8

Modern treatments such as hematopoietic stem cell transplantation (HSCT) are complex and costly due to limited medical facilities and a scarcity of HLA-matched donors. ⁸Consequently, we propose that preventing thalassemia through proactive measures is a more effective strategy.

In India, where approximately 3-4% percent of the population are carriers, 10,000-15,000 children with Thalassemia Major are born annually due to insufficient awareness. This knowledge gap leads to a critical survival rate, as highlighted by the Mumbai carrier screening program’s 20year report. Successful premarital screening programs in various countries, such as Italy, Greece, Canada, Great Britain, and Cyprus have been effective in preventing thalassemia. While Cyprus has seen a reduction in thalassemia prevalence through compulsory prenatal screening, cultural and ethnic factors worldwide contribute to the increasing population of affected individuals.⁹

The Ithagenes (https://www.ithanet.eu/db/ithagenes) database has reported nearly 3447 entries involving the β-globin gene. However, small deletions that remove all or part of the β-globin gene are rare. Some βthalassemia are caused by deletions or mutations in the regulatory regions upstream of the β-globin gene complex. The β-globin gene mutation was detected using PCR to amplify fragments and sequence analysis. Automated DNA sequencing employing the dye terminator method is preferably used for the complete sequencing of the whole β-globin gene.

Notable mutations in India are IVS1-5 (G→C), which are often found in a homozygous state or in combination with other β-thalassemia mutations.¹⁰Another prevalent mutation is codon 15 (G→A), which is observed in both homozygous and compound heterozygous states with other β-thalassemia mutations.¹¹ The codon 41/42 (-TCTT) mutation is also common and presents in homozygous or compound heterozygous forms. In addition, the IVS1-1 (G→T) mutation is noteworthy and is often found in a homozygous state or in combination with other β-thalassemia mutations.¹²