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

Dominant inherited β-thalassemias describe those β-thalassemia variants that result in a thalassemia intermediate phenotype in individuals who have inherited only a single copy of the abnormal β 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 β-thalassemia. We describe a case of inclusion body β-thalassemia in a 51-year-old Spanish male caused by a deletion of 11 bp (CD 131–134) in exon 3 of the β-globin gene. The deletion of 11 bp in exon 3 of the β-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 α1β1 contact and α1β2 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 β-thalassemia mutation.