Two novel mutations in the 3' untranslated region of the beta-globin gene that are associated with the mild phenotype of beta thalassemia.

INTRODUCTION: There are approximately 800 different genomic alterations of the ß-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we have identified two novel putative mutations (HBB:c.*+108 A>G and HBB:c.*+132 C>T) in the 3' untranslated region (3'-UTR) of the ß-globin gene and describe their clinical implications. METHODS: Four patients from two unrelated families, all with hematological and clinical features associated with beta-thalassemia (ß-thal), and their family members were included. The molecular diagnoses of the ß-globin gene mutations were performed by direct sequencing. RESULTS: A novel mutation, HBB:c.*+108 A>G, was found in combination with the IVS-I-110 G>A (HBB:c.93-21 G>A) mutation in three siblings (two brothers and one sister) from one of the families involved in our study. Their mother was found to be a carrier for HBB:c.*+108 A>G with normal HbA2 levels. The other novel mutation, HBB:c.*+132 C>T, was found in combination with IVS-I-1 G>A (HBB:c.92 + 1G>A) in a 7-year-old boy diagnosed as ß-thal intermedia from the second family. His father and two brothers were all carriers of HBB:c.*+132 C>T with borderline HbA2 levels. CONCLUSION: Based on the observed ß-thal intermedia phenotypes and the accompanying mutations, we conclude that these novel ß-globin gene 3' UTR mutations are associated with the mild phenotype of ß-thal.