SILENT CARRIER BETA-THALASSEMIA DUE TO A SEVERE BETA-GLOBIN MUTATION INTERACTING WITH OTHER GENETIC ELEMENTS

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