Haema 2011; 2(3): 225-234
by Joanne Traeger-Synodinos1, Christina Vrettou1,2, Manousos Papadakis3, Emmanuel Kanavakis1,2
1Laboratory of Medical Genetics, University of Athens, Choremeio Research Laboratory,
2Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Aghia Sophia’s Children’s Hospital, Athens,
3Laboratory for Prenatal Diagnosis, Laiko Hospital, Athens, Greece
Abstract
The thalassemia syndromes are the most common monogenic disorders worldwide, with an estimated 270 million heterozygotes worldwide, and are caused by a wide range of underlying defects.The globin genes are located in two multigene clusters. The α-globin gene cluster, is located near the telomere of the short arm of chromosome 16 (16p13.3) and the β-globin gene cluster is located on the short arm of chromosome 11 (11p15.5). The genes in both clusters are arranged in the order of which they are ontologically expressed. Over 1000 mutations within or around the α- and β-globin genes have been observed, affecting either the quantity or quality of the globin chains synthesized. Mutations in other regions of the genome, either in other erythroid-specific genes or in genes more generally involved in controlling gene expression, have also been observed to influence the expression of globin genes and consequently the synthesis of globin chains. Finally there are rare examples of acquired forms of α-thalassemia caused by somatic mutations in patients with myelodysplastic syndromes.