Molecular analysis of a Thai β-thalassaemia heterozygote with normal haemoglobin A 2 level: implication for population screening

Abstract

Background This study aimed to characterize the molecular basis of a β-thalassaemia heterozygote who had a normal haemoglobin A₂ level. Methods Using haematological and molecular analyses, the -α and β-globin genotypes in a Thai woman with normal haemoglobin A₂ level, who was identified in a thalassaemia and haemoglobinopathy screening programme, were examined. Results The patient was positive for a 0·36% one-tube osmotic fragility test but negative for the dichlorophenolindophenol dye test for haemoglobin E. Haemoglobin A and A₂ were observed on cellulose acetate electrophoresis with the haemoglobin A₂ of 2·0%, compatible with an α-thalassaemia 1 carrier. Polymerase chain reaction analysis failed to detect α-thalassaemia 1 (South East Asian deletion). β-globin gene analysis detected a severe β^o-thalassaemia allele with the 4 bp (-CTTT) deletion at codons 41/42. Further analysis of the-globin gene identified the homozygosity of the 3·7 kb deletion α-thalassaemia 2. Conclusions The patient was found to be an unusual case: a β^o-thalassaemia carrier with a low haemoglobin A₂ concentration, in combination with a homozygosity for the 3·7 kb α-thalassaemia 2 deletion. The approach used to characterize the patient and the result obtained in this report will prove useful for population screening of thalassaemia in regions where both α- and β-thalassaemias are common.