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Phenotypic expression of H b F in common high H b F determinants in T hailand: roles of α‐thalassemia, 5′ δ‐globin BCL 11 A binding region and 3′ β‐globin enhancer
Author(s) -
Prakobkaew Nattaphol,
Fucharoen Supan,
Fuchareon Goonnapa,
Siriratmanawong Nirut
Publication year - 2014
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12201
Subject(s) - thalassemia , microbiology and biotechnology , genotype , phenotype , alpha thalassemia , fetal hemoglobin , biology , gene , genetics , fetus , pregnancy
Background Deletions of δ‐ and β‐globin genes are associated with different H b F levels. To address this, we have examined hematological and molecular characteristics in a large cohort of high H b F determinants in T hailand. Methods A total of 160 unrelated adult subjects with heterozygous trait for high H b 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 H b ( 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 H b E ‐β 0 ‐thalassemia were found to be compound H b E ‐δβ 0 ‐thalassemia. Differences in hematological features as well as H b F levels were noted and are presented comparatively. Conclusion Comparison of phenotypes, genotypes, and the deletion breakpoints of these T hai high H b F determinants indicates that differences in H b F expression are correlated with the existence of α‐thalassemia, the loss of BCL 11 A binding region located 5′ to the δ‐globin gene and the 3′ β‐globin enhancer, which confirms their important roles in fetal H b expression.