Filipino β0 thalassaemia: A high Hb A2 β0 thalassaemia resulting from a large deletion of the 5′ β globin gene region

Abstract

A large novel deletional β0 thalassaemia mutation associated with unusually high levels of haemoglobin (Hb) A2 in heterozygotes is described in two unrelated subjects of Filipino background. The deletion was characterised by DNA mapping including pulsed field gel electrophoresis. Filipino β0thalassaemia extends for approximately 45 kb beginning approximately 1.5 kb 3′ to the δ globin gene. It is the largest deletion to date which gives rise to the β0 thalassaemia phenotype. This mutation, similar to previously described deletional β0 thalassaemias associated with high Hb A2, removes sequences 5′ to the β globin gene promoter and emphasises the functional importance of the 5′ β globin region in eliciting the unusually high level of Hb A2. This example also suggests that it is the 3′ sequences which are transposed rather than the actual deletion size which are significant in the raised fetal haemoglobin (Hb F) found with some of the thalassaemias.