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

Abstract

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