Molecular characterisation of mutations giving rise to β-thalassemia in Vietnam

Introduction: Thalassemias (thal) are the most common monogenic diseases worldwide. The spectrum of β-thal mutations among Vietnamese populations indicates a noticeable heterogeneity.Purpose: to define the molecular basis of mutations affecting β-globin gene in Central Vietnam, and the phenotype/genotype relationship in β-thal patients.Patients and methods: 226 subjects (138 β-thal carriers, 57 patients affected by β-thal intermedia and 31 affected by β-thal major) were examined by sequencing of β-globin genes. 88 patients were evaluated for α-thal genes and the -158(C>T) polymorphism at the Gγ-globin gene.Result: 12 mutations were observed. Four resulted the most common: the HbE, cd 17(A>T), cds 41/42(-TTCT) and IVS-I-1(G>T) accounting for 86.94%. Less frequent were: cds 71/72(+A), -28(A>G), cd 95(+A), cd 26(G>T), observed in 11.46% of chromosomes, whereas the -198(A>G), -72(T>A), -50(G>A) and cds 14/15 (+G) resulted rare. The βE/βE, βE/β+, β+/β+ genotypes were observed in mildly affected patients, whereas the βo/βo resulted limited to thal major ones. The coinheritance of α-thal undoubtedly ameliorates the severity of the disease. No clear correlation was observed between -158 (C>T) Gγ polymorphism and severity of β-thal.Conclusion: The allelic frequencies of β-thal mutations observed in Central Vietnam appears to be quite different with respect to those observed in other Vietnamese regions as well as to SEA countries. These results will impact future large screening campaigns.