Abstract:
INTRODUCTION
Beta thalassemia major is a severe genetic blood disorder caused by mutations in the HBB
(beta-globin) gene, leading to defective haemoglobin production, chronic anaemia, and severe
complications such as growth retardation, splenomegaly, and iron overload due to frequent
blood transfusions. It is an autosomal recessive disorder that predominantly affects
populations with high rates of consanguinity, including regions like North Karnataka. The
management of beta thalassemia major involves lifelong blood transfusions, iron chelation
therapy, and, in some cases, hematopoietic stem cell transplantation (HSCT). Despite these
therapeutic advancements, a better understanding of the genetic mutations and polymorphisms
associated with the disease can help improve treatment strategies, prognosis, and genetic
counselling.1
Beta thalassemia is caused by a wide range of mutations in the HBB gene, located on
chromosome 11, that disrupt beta-globin chain synthesis. These mutations are highly
heterogeneous and vary across different ethnic and geographical populations. While some
mutations result in the complete absence (β⁰) of beta-globin production, others lead to a partial
reduction (β⁺) in its synthesis. In India, more than 30 common mutations have been reported
in beta thalassemia patients, with IVS1-5(G>C), IVS1-1(G>T), and 619-bp deletion being
among the most prevalent.2 However, apart from these major mutations, single nucleotide
polymorphisms (SNPs) and variations in specific regions such as exon 2 of the HBB gene may
also influence the severity and clinical manifestations of the disease.
Polymorphisms in the HBB gene, particularly in exon 2, have been of growing interest in
recent research. Exon 2 encodes a critical segment of the beta-globin polypeptide chain, and
variations in this region may affect haemoglobin function, disease severity, and treatment
response. Some polymorphisms might lead to modifications in haemoglobin stability,
