The role of HBG2, BCL11A, and HBS1L-MYB in early diagnosis of transfusion-dependent thalassemia among Egyptian children

Abstract

Background Hereditary hemoglobinopathies are the most frequent diseases accountable to a single gene defect. Common mutations of the beta-globin gene are detected by PCR-based techniques. Objective To evaluate the role of HBG2, BCL11A, and HBS1L-MYB polymorphisms in addition to Thalassemia Severity Score (TSS) in the early diagnosis of transfusion-dependent thalassemia patients among Egyptian children and their impact on clinical decision. Patients and methods Thalassemia mutation analysis was performed by the Beta-Thal Modifier Strip Assay to determine the five polymorphisms associated with severity, and an automated online calculator (TSS). Results The transfusion-dependent group showed significantly higher TSS (P<0.001), with a sensitivity of 75%, specificity of 95%, positive predictive value of 93.8%, negative predictive value of 79.2%, and an accuracy of 85%. HBG2 CT and CC genotypes were significantly associated with younger age of first transfusion and higher transfusion rates. Deletion in alpha gene was significantly associated with TT genotype, followed by GG and then GT. TSS decreased gradually through wild, heterozygous, and homozygous rs7482144 and rs1427407 genotypes. Transfusion-free survival tends to decrease gradually with increased TSS severity (P<0.001). The HBS1L-MYB rs9399137 TC genotype was associated with poor transfusion-free survival by Cox regression analysis. Beta phenotype mild/mild, mild/severe, rs7482144 CT, TT, and rs1427407 GT, TT were associated with the protective effect against higher severity. Conclusion HBG2, BCL11A, and HBS1L-MYB have an important role in early diagnosis and prognosis of transfusion-dependent thalassemia among Egyptian children.