Molecular Study in Identifying Genotypes to Phenotypes Relations of Transfusion-Dependent Thalassemia Patients in Cirebon, West Java

Abstract

Molecular characterization is important prior to clinical management as it can provide additional information for the clinical management of patients. This study aims to characterize the most common mutation and identify genotype-to-phenotype relations in transfusion-dependent thalassemia patients. A total of 30 transfusion-dependent patients were recruited who had never undergone thalassemia detection. Peripheral blood samples were collected and analyzed for hematological parameters, hemoglobin component, and HBA and HBB gene mutation analysis. The most common mutation in the HBB gene was IVS1-5 (41.7%) and CD26/HbE (23.3%), with homozygous IVS1-5 (23.3%) and IVS1-5/HbE (30%) as the most common genotype. The study revealed a genotype and phenotype correlation of the most common thalassemia mutations in Cirebon, West Java, Indonesia, with four alleles dominating the genotype, covering 88.4% of the population. A significant difference in HbA2+HbE and HbF levels was observed between homozygous ?-thalassemia and ?-thalassemia/HbE. Homozygous ?-thalassemia with ?-thalassemia trait has better hematological parameters compared to homozygous ?-thalassemia and ?-thalassemia/HbE but does not translate to a better severity index. Characterizing the most common thalassemia mutations in the Indonesian population can streamline the subsequent diagnostic approaches by focusing on the small range of predominant alleles instead of a wide range of alleles, which can provide critical data for better patient management.