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

Abstract

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 δβ(0) -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 δβ(0) -thalassemia (n = 79), 79 kb deletion hereditary persistence of fetal Hb (HPFH)-6 (n = 65), Indian deletion-inversion (G) γ((A) γδβ)-thalassemia (n = 15) and 78 kb deletion Chinese (G) γ((A) γδβ)-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-β(0) -thalassemia were found to be compound Hb E-δβ(0) -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.

Keywords: BCL11A binding region; Hb F expression; denaturing high-performance liquid chromatography; hereditary persistence of fetal hemoglobin; δβ-thalassemia.