The Key Genetic Determinants Behind the Phenotypic Heterogeneity of HbE/β-thalassemia Patients and the Probable Management Strategy

Abstract

HbE/β-thalassemia is the most common severe form of thalassemia which is very prominent in South East Asian countries. It is responsible for nearly one-half of all the severe types of β-thalassemia all over the world. It is also known to represent a wide range of phenotypic diversity which varies from asymptomatic to transfusion-dependent severe phenotype. The most important predictive factor is mutations within the beta-globin gene (HBB). Apart from the primary genetic modifiers, there are certain other determinants regulating the phenotypic heterogeneity including, co-inheritance of alpha thalassemia mutations and other secondary modifiers including Xmn1 polymorphism, HBS1L-MYB, GATA-1, BCL11A polymorphism, and presence of HPFH mutations. Although the degree of severity is also determined by other tertiary genetic modifiers like increase in serum erythropoietin due to anemia, previous infection with malaria, environmental factors, splenectomy, etc. This review aimed to reveal the potential genetic predictors of HbE/β-thalassemia patients and the probable management strategy. This also enhances the generation of “personalized medicine” for better patient care. The instability of clinical phenotype and remarkable variation indicate careful monitoring of treatment for each patient and the therapeutic approaches should be monitored over time.