Silent carrier β-thalassaemia due to a severe β-globin mutation interacting with other genetic elements

Beta-thalassaemia is caused by the presence of two mutated β-globin genes, one inherited from each parent. We describe two families in which the diagnosis of β-thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier β-thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe β-thalassaemia phenotype. In one case, concurrent deletional α-thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier β-thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia.