Study on hemoglobinopathies in central provinces of Vietnam

The Vietnamese population is ethnically highly heterogeneous and the spectrum of β-thalassemia alleles is slowly defining. On the whole, six mutations of the β0- and a mutation of the β+- thalassemia have been identified and observed with distinct incidence in the different areas.Interaction between these mutations and the rather common Hb E leads to a variety of thalassemia syndromes, in particular to the severe forms of homozygous β-thal and Hb E-β-thal diseases. Nonetheless, epidemiological data is still insufficient and fragmented. In this Doctoral Thesis, a screening program for hemoglobinopathies was carried out in the central provinces of Vietnam as part of the ongoing cooperation between the Universities of Hue and Sassari.A study group of 160 subjects referred to Hue Medicine and Pharmacy College and PhuVang District Hospitals for hematological and clinical evaluation and a control group of 193 individuals were included in the study. A total of 89 samples showed abnormal hematological parameters and have undergone to Hbpathies screening. About 30% of them, having qualitative or quantitative alteration in Hb profiles, were investigated by DNA analysis.Several mutated β-alleles were identified by nucleotide sequencing. Some of them were already described also in other countries of the Southeast Asia with different incidence. On the contrary, the β+ promoter mutation -72 (T→A), found in a 5-year old child and in his relatives, has never been described before. In vitro expression studies were performed into K562 cells. The transcriptional activity of the mutated promoter is roughly half that of the wild type promoter.Although this is a mild thalassemic mutation, it is impossible to predict the severity of the phenotype and its clinical implications in the interaction with severe β-thalassemic allele. Indeed, because of the extremely high gene frequency for HbE and the widespread occurrence of β- thalassemia in Vietnam, the incidence of βE/βThal or βThal/βThal compounds is very high.This result underline the importance of identifying and characterizing new or rare β-thalassemic alleles in carrier screening and prenatal diagnosis in order to reduce the burden of thalassemias, avoid unnecessary transfusions in TI and start early transfusions in TM.