Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-β-thalassemia in Northeast Thailand

Hb E-β-thalassemia is the most common form of β-thalassemia found in Thailand. The disease exhibits a varied clinical expression ranging from severe transfusion dependence to relatively mild thalassemia intermedia. We evaluated the effects of primary and secondary genetic factors in modulating the hematological and clinical presentation of 148 northeast Thai patients including 103 severe thalassemia major (TM) and 45 thalassemia intermedia (TI). Among 148 cases examined, eleven different mutations including two novel ones; (β33/34 (− G) and βIVS2#815 C–T) were identified in trans to the βE gene in two TM cases. The other 9 known mutations included β41/42, β17, βIVS2#654, β− 28, β71/72, β35, βIVS1#5, βIVS1#1 and β41. Except for the β− 28 mutation which was found only in the TI group, others mutations were identified in both TM and TI. Co-inheritance of α-thalassemia as a phenotype modulating factor was not evident in this study, nor was the presence of the − 158 Gγ-globin Xmn I polymorphism. Further analysis of the polymorphic (TG)n(CG)m repeats within the IVS2 of the two γ-globin genes revealed no different proportions of the polymorphic patterns among TM and TI groups of patients either. Our data reveals that in the majority of these Hb E-β-thalassemia patients, it is very hard to predict the clinical phenotype of the patients from the β-globin mutations and these secondary genetic modifiers.