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 beta-thalassemia and describe hematological features among different mutations and the concurrent of alpha- and beta-thalassemias, 849 unrelated beta-thalassemia heterozygotes recruited in northeast Thailand during a prevention and control program were studied. beta- and alpha-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 beta degrees- and beta(+) -thalassemias were identified. Eight of these 17 beta-thalassemia alleles accounted for 97.4%, others were found at lower frequencies (<1.0%). Of the 849 cases, 626 were investigated for common alpha-thalassemia mutations and 155 (24.8%) were found to be co-inherited with different forms of alpha-thalassemia. Comparison of the hematological parameters among different beta-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 A(2) and Hb F levels in individuals with the 3.4 kb deletion were significantly higher than those with other mutations. Interaction of each beta-thalassemia mutation with alpha-thalassemia did not affect the diagnostic ranges of Hb A(2) and Hb F, though the significantly increased MCV and MCH was noted. These findings underline the heterogeneity of beta-thalassemia and the importance of hematological and molecular analyses of both alpha-and beta-thalassemias in the diagnosis and genetic counseling of the couples at-risk of having babies with severe thalassemia diseases in the region. (C) 2011 Elsevier Inc. All rights reserved.