Thalassemia — From Genotype to Phenotype

Abstract

Abstract Thalassemia encompasses serious diseases with complex pathophysiology that is difficult to explain since it is considered a group of defects with similar clinical effects, still not a single disorder. Understanding genetic factors contributing to the pathophysiology of thalassemias has enabled the identification of causative genes and development of diagnostic tests, helping defuse the confusion that evolves from clinical descriptions alone and correlating clinical symptoms with thalassemia disease. More than 300 disease-causing mutations have been identified so far, mostly behaving as Mendelian recessives, however, there are variants that cause a disease phenotype even when present in a single copy. The remarkable technical developments of molecular biol‐ ogy gradually make it possible to define many of the globin gene molecular underlying pathologies. Still, current morbidity and mortality remain unacceptable underlining the need for fur‐ ther research in this area. In this chapter, we have summarized the current state of knowledge in the field of molec‐ ular lesions that underlie thalassemias, how they relate to their phenotypes, as well as the importance of conveying to the reader the extent to which it is possible to explain their clinical heterogeneity at the molecular level. Keywords: