The effect of the beta thalassemia mutation on the clinical severity of the sickle beta thalassemia syndrome.

In this study, we have defined the beta thalassemia mutation and characterized the beta globin haplotype and the alpha globin gene arrangement in a group of patients of Sicilian descent with beta (s)/beta thalassemia. We found that those patients carrying a beta(+) thalassemia mutation associated with a moderate reduction of beta chain synthesis (beta(+) IVS-1 nt 6) have normal or reduced Hb levels and mild to moderate clinical manifestations, as defined by the number of hospital admission and sickle cell crises per year. Those patients carrying a beta(+) thalassemia mutation associated with a severe reduction of beta chain synthesis (beta(+) IVS-1 nt 110) have a disease of moderate severity. In those carrying a beta(0) thalassemia gene the disease was clinically very heterogeneous, ranging in severity from mild to severe with no difference related to the type of mutation [beta(0) 39, beta(0) IVS-1 nt 1, beta(0) IVS-2 nt 1, beta(0) 6 (-1bp)]. In this last group of patients part of the clinical variability may be attributed to the HbF levels, which were higher in those with mild to moderate clinical severity.