A deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene produces the phenotype of inclusion body beta-thalassemia

Dominant inherited beta-thalassemias describe those beta-thalassemia variants that result in a thalassemia intermediate phenotype in individuals who have inherited only a single copy of the abnormal beta gene. This form of thalassemia is characterized by moderately severe anemia with jaundice and splenomegaly; it is also characterized by the presence of inclusion bodies in the red blood cell precursors and has, therefore, previously been referred to as inclusion body beta-thalassemia. We describe a case of inclusion body beta-thalassemia in a 51-year-old Spanish male caused by a deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene. The deletion of 11 bp in exon 3 of the beta-globin chain is predicted to produce an anomalous chain of 134 Amino acids instead of the normal 146 with an extremely altered amino acid sequence from residues 131-134. Although this shortened variant would lead to a missing H helix, which is involved in alpha1beta1 contact and alpha1beta2 subunit interactions, the variant chain can still be bound to the heme group and acquire a secondary structure that is not suitable for the formation of stable dimers or tetramers and also less susceptible to proteolytic degradation. This is the first report of such a beta-thalassemia mutation.