Molecular Characterization of δβ-Thalassemia and Hereditary Persistence of Fetal Hemoglobin in the Indian Population

Abstract

delta beta-Thalassemia (delta beta-thal) and hereditary persistence of fetal hemoglobin (HPFH) are heterogeneous disorders characterized by elevated levels of Hb F in adult life. The two disorders should not be considered as unambiguously separate entities but rather as a group of disorders with a variety of partially overlapping phenotypes. This study was undertaken to determine the hematological and molecular characteristics of high Hb F determinants among Indians. A gap-polymerase chain reaction (gap-PCR)-based approach was used for molecular characterization of high Hb F phenotypes. Fifty-five unrelated individuals were studied. The molecular findings were correlated with the hematological data. DNA analysis identified the deletion-inversion (G)gamma((A)gamma delta beta)(0)-thal in 15 cases (27%) and the HPFH-3 (Indian deletion) determinant in 26 cases (47.2%) and the Vietnamese/Chinese determinant (27 kb deletion) in five cases (9%), which is being reported for the first time from India; 16% (nine cases) of the samples remained uncharacterized. This study emphasizes that delta beta-thal and HPFH determinants are common in India. Molecular analysis will aid in understanding genotype-phenotype correlations and will facilitate prevention and control programs of thalassemia and hemoglobinopathies in this region.