Mutational and Functional Impact of β-globin Gene Mutation in Indonesian Thalassemia Patients using in Silico Method

Introduction Indonesia is located along the “Thalassemia Belt,” a hotspot region for hemoglobinopathies, including beta thalassemia, with approximately 3–10% of the Indonesian population diagnosed with this disease. Thalassemia was diagnosed using the Hb analysis results. However, the single nucleotide variant (SNVs) database for the Indonesian population, which leads to β-thalassemia disease, has not been extensively studied. This study aimed to profile the genetic variations in Indonesian β-thalassemia patients and conduct in silico characterization of their functional effects. Methods Twenty thalassemia patients were recruited for this study. The sample collected from the respondents was whole blood in EDTA tubes, with a minimum collection time of 14 days after blood transfusion. Genomic DNA (gDNA) was extracted using a commercial kit, directly amplified using Polymerase Chain Reaction (PCR) with specific primers for β-globin and sequenced using Sanger Sequencing. All variants located in exon regions were analyzed using FinchTV, BioEdit, and Biovia Discovery Studio to determine their functional impact. Results Ten reported pathogenic variants were observed along with one rare variant. Genetic variations found according to its common name and nomenclature based on Human Genome Variation Society (HGVS) are IVS1nt.1 (HGVS: c.92+1G>A), IVS1nt.1 (HGVS: c.92+1G>T), IVS1nt.2 (HGVS: c.92+2G>T), IVS1nt.5 (HGVS: c.92+5G>C), IVS2nt.654 (HGVS: c.316-197C>T), Cd15 (HGVS: c.47G>A), Cd26 (HGVS: c.79G>A), Cd30 (HGVS: c.92G>C), Cd41/42 (c.126_129delCTTT), and Cd35 (HGVS: c.110delC). Analysis of amino acid interactions revealed that disease-causing mutations were clinically relevant in each subject. Conclusions This study has bioinformatically proven the effect of genetic mutations and predicted their effect on amino acid interactions. These findings contribute to the study of Indonesian thalassemia and require further research.