Unraveling the Genetic Landscape: Frequency of Beta Globin Genes Mutations in Transfusion-Dependent Beta Thalassaemia Patients at an Urban Centre in Karachi

Abstract

Objective: To identify the frequency of mutations in transfusion dependent beta thalassaemia patients presenting at a single urban thalassaemia center in Karachi.

Methodology: This single- center study was conducted at the Muhammadi Blood Bank and Diagnostics Center and Baqai Medical University, Karachi. A total of 100 patients diagnosed with transfusion dependent beta thalassaemia were enrolled in this study. Amplification Refractory Mutation System - Polymerase Chain Reaction (ARMS-PCR) was used for a genetic analysis of 12 beta thalassaemia mutations, namely, Fr 8-9(+G ), IVS I-5(G-C), Fr 41-42(-TCTT), IVS I-1(G-T), Del 619 bp, Cd-5 (-CT), Fr 16 (-C), Cd-15 (G-A,), Cd-30(G-C), Cd-30 (G-A), IVS II-1 (G-A), and Cap+ 1 (A-C).

Results: The Cd-5 (-CT) mutation was the most common beta thalassaemia mutation in our study population accounting for 37.4% mutated alleles, followed by Fr 8-9(+G) at 20.9%, Del 619 bp at 9.2% and Fr 16 (-C) at 8.6% cases. Out of 100 ?-thalassaemia patients, 37% were identified as homozygous, while 63% were classified as compound heterozygous for thalassaemia mutations. A total of 10 different beta thalassaemia mutations were identified, distributed across 26 distinct genotypes. The most common genotype observed was compound heterozygous Fr 8-9(+G)/ Cd-5 (-CT), with a frequency of 25%. This was succeeded by homozygous Cd-5 (-CT), compound heterozygous Del619bp/Fr16(-C), and homozygous IVSI -1(G-T), which represented 19%, 6%, and 6% of cases, respectively.

Conclusion: Our study provides an extensive overview of mutational analysis of thalassaemia gene in transfusion dependent beta thalassaemia patients. The most frequently detected mutation was Cd-5 (-CT). We observed variation in the frequency of known mutations, emphasizing the intricate genetic makeup of thalassaemia disorder within our population.