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' ß-globin enhancer.

BACKGROUND: Deletions of δ- and ß-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 δß(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 δß(0) -thalassemia (n = 79), 79 kb deletion hereditary persistence of fetal Hb (HPFH)-6 (n = 65), Indian deletion-inversion (G) γ((A) γδß)-thalassemia (n = 15) and 78 kb deletion Chinese (G) γ((A) γδß)-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-ß(0) -thalassemia were found to be compound Hb E-δß(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' ß-globin enhancer, which confirms their important roles in fetal Hb expression.

Secondary erythrocytosis caused by hemoglobin Tak/(뫧)0-thalassemia syndrome.

Secondary erythrocytosis may arise from several causes, but an association with oxygen transport is rare. We describe for the first time a form of secondary erythrocytosis caused by compound heterozygosity for hemoglobin (Hb) Tak and (δß)(0)-thalassemia found in an adult Thai individual. The patient had marked erythrocytosis and microcytosis with increased Hb and hematocrit values. Hb analyses using the Hb Gold Analyzer showed Hb A2 (72.5%) and Hb F (30.0%) without Hb A while the capillary electrophoresis revealed 2.3% Hb A2 and a major peak of Hb F (91.2%). Further molecular investigation identified that he was in fact a compound heterozygote for Hb Tak and deletional (δß)(0)-thalassemia. Hematological parameters of the patient were compared with those observed for a Thai boy who demonstrated features of erythrocytosis and microcytosis caused by homozygous Hb Tak with α(+)-thalassemia and with those of pure carriers of Hb Tak and (δß)(0)-thalassemia in our series. This report confirms the importance of both Hb and molecular investigations for the assessment of genotype/phenotype correlation and the appropriate management of the patients.