Phenotypic expression of Hb F in common high Hb F determinants in Thailand: Roles of α-thalassemia, 5' δ-globin BCL11A binding region and 3' β-globin enhancer

摘要

Background: Deletions of δ- and β-globin genes are associated with different Hb F levels. To address this, we have examined hematological and molecular characteristics in a large cohort of high Hb F determinants in Thailand. Methods: A total of 160 unrelated adult subjects with heterozygous trait for high Hb F determinants and another 10 patients with compound heterozygous trait for Hb E were selectively recruited. Hematological parameters and Hb analysis were recorded, and α-thalassemia mutations were investigated. DNA deletions causing δβ0-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) were identified using multiplex PCR and denaturing high-performance liquid chromatography (HPLC) assays developed. Results: Four different DNA deletions were detected including the 12.6 kb deletion δβ0-thalassemia (n = 79), 79 kb deletion hereditary persistence of fetal Hb (HPFH)-6 (n = 65), Indian deletion-inversion Gγ(Aγδβ)-thalassemia (n = 15) and 78 kb deletion Chinese Gγ(Aγδβ)-thalassemia (n = 1). Eighteen cases were found to carry α-thalassemia with 10 different genotypes. All 10 patients who had similar hematological phenotype with that of Hb E-β0-thalassemia were found to be compound Hb E-δβ0-thalassemia. Differences in hematological features as well as Hb F levels were noted and are presented comparatively. Conclusion: Comparison of phenotypes, genotypes, and the deletion breakpoints of these Thai high Hb F determinants indicates that differences in Hb F expression are correlated with the existence of α-thalassemia, the loss of BCL11A binding region located 5' to the δ-globin gene and the 3' β-globin enhancer, which confirms their important roles in fetal Hb expression.