Genetic Mutations and Clinical Severity in Hemoglobin E/Beta-Thalassemia Patients in Bangladesh.

Background and objective The phenotypically diverse presentation of hemoglobin (Hb) E/β-thalassemia is often attributed to coinheritance of β-globin (HBB) gene mutations. This study aimed to describe the genetic mutations and clinical severity of HbE/β-thalassemia patients from low-resource settings. Methods A total of 32 HbE/β-thalassemia patients were included in this cross-sectional study. Cases were confirmed by capillary Hb electrophoresis or high-performance liquid chromatography and were further analyzed alongside clinical information and ancestral data. The data collection period spanned from May 2019 to July 2020. Gene sequencing was performed using the Sanger sequencing method for mutational analysis, and Mahidol scoring was applied to assess clinical severity. Results The median age of the patients was 20 years (interquartile range (IQR): 17-22.5). Phenotypically, mild, moderate, and severe disease were observed in 12 (37.5%), 14 (43.8%), and six (18.8%) patients, respectively. Overall, 13 heterozygous mutations were identified in the HBB gene. Among these, IVS-1-5 (G>C) was the most common mutation (n = 17, 53.1%), and codon 30 (G>C) (n = 4, 12.5%) was the second most common mutation. The IVS-1-5 (G>C) mutation was significantly more frequent among patients with severe disease (p<0.001). Conclusions This study is one of the few to characterize clinical severity and genetic mutations in HbE/β-thalassemia patients in Bangladesh. The information on clinical severity patterns could be useful for determining service priorities and ensuring the proper allocation of limited resources.