Genotype and phenotype characterizations in a large cohort of β-thalassemia heterozygote with different forms of α-thalassemia in northeast Thailand

In order to update the molecular basis of β-thalassemia and describe hematological features among different mutations and the concurrent of α- and β-thalassemias, 849 unrelated β-thalassemia heterozygotes recruited in northeast Thailand during a prevention and control program were studied. β- and α-thalassemia mutations were investigated using the polymerase chain reaction (PCR)-based technologies and hematological parameters were recorded using standard methods. Seventeen different mutations including both β0- and β+ -thalassemias were identified. Eight of these 17 β-thalassemia alleles accounted for 97.4%, others were found at lower frequencies (< 1.0%). Of the 849 cases, 626 were investigated for common α-thalassemia mutations and 155 (24.8%) were found to be co-inherited with different forms of α-thalassemia. Comparison of the hematological parameters among different β-thalassemia mutations revealed an increasing trend of MCV and MCH in a group of heterozygous states for the 3.4 kb deletion and the A-G substitution at nucleotide (NT) -28. Hb A2 and Hb F levels in individuals with the 3.4 kb deletion were significantly higher than those with other mutations. Interaction of each β-thalassemia mutation with α-thalassemia did not affect the diagnostic ranges of Hb A2 and Hb F, though the significantly increased MCV and MCH was noted. These findings underline the heterogeneity of β-thalassemia and the importance of hematological and molecular analyses of both α-and β-thalassemias in the diagnosis and genetic counseling of the couples at-risk of having babies with severe thalassemia diseases in the region.