Association of α globin gene quadruplication and heterozygous β thalassemia in patients with thalassemia intermedia

Ten patients with thalassemia intermedia with variable severity and apparent simple heterozygosis for b0 39 C>T nonsense mutation were submitted to clinical, hematologic and molecular studies. The presence of an unknown molecular defect (silent b-thalassemia) unlinked to the b cluster interacting with the heterozygous b thalassemia, was previously postulated in these families. Analysis of the a globin gene cluster with PCR-based methods (MLPA, GAP-PCR, digestion with restriction enzymes) detected complex rearrangements in the a cluster. A duplication of the a globin gene locus, including the upstream regulatory region, was present in all the patients, associated in some of them with deletion or non-deletion a thalassemia. The variability of the clinical phenotype correlates with the degree of the globin chain imbalance. The presence of a globin cluster duplication should be considered in patients heterozygote for b-thalassemia with thalassemia intermedia phenotype and in the carriers of suspected silent b thalassemia. Key words: thalassemia intermedia, a-globin gene quadruplication, silent b thalassemia, MLPA. Citation: Sollaino MC, Paglietti ME, Perseu L, Giagu N, Loi D, and Galanello R. Association of a globin gene quadruplication and heterozygous b thalassemia in patients with thalassemia intermedia. Haematologica 2009.94:1445-1448. doi: 10.3324/haematol.2009.005728 ©2009 Ferrata Storti Foundation. This is an open-access paper.