Annotated Definition of BCL11A and HMIP-2 Haplotypes Through The Analysis of Sicilian ?-Thalassemia Patients with High Levels of Fetal Hemoglobin.

Fetal hemoglobin (Hb F) is the principal ameliorating factor of ?-thalassemia (?-thal) and sickle cell disease. Persistent production in adult life is a quantitative trait regulated by loci inside or outside the ?-globin gene cluster. From genome-wide association studies, principal quantitative trait loci (QTL) (accounting for 50.0% of Hb F variability in different populations) have been identified in the BCL11A gene, HBS1L-MYB intergenic polymorphism and the ?-globin gene cluster itself. In this study, we analyzed quantitative trait haplotypes in two Sicilian families with extremely mild ?-thal and unusually high Hb F expression, in order to examine possible genetic background variations in a similar ?-thalassemic phenotype. This study redefines the linkage disequilibrium blocks at these loci, but also shows slight differences between probands in haplotype combinations which could reflect different mechanisms of high Hb F production in patients with ?-thal. We proposed a haplotype-based approach as a useful tool for the understanding of ?-thal phenotype variation in patients with similar ?-thalassemic backgrounds in an attempt to answer the recurring question of why patients with the same ?-thalassemic genotype show different phenotypes. Read More: http://informahealthcare.com/doi/abs/10.3109/03630269.2013.800823