Two novel mutations in the 3′ untranslated region of the beta- globin gene that are associated with the mild phenotype of beta thalassemia T. BILGEN*, O. A. CLARK † , Z. OZTURK ‡ , M. AKIF YESILIPEK ‡ , I. KESER* *Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya, Turkey † Department of Medical Genetics, Faculty of Medicine, Akdeniz University, Antalya, Turkey ‡ Department of Pediatric Hematology and Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey Correspondence: Turker Bilgen, PhD, Department of Medical Biology and Genet- ics, Faculty of Medicine, Akde- niz University, 07059-Antalya, Turkey. Tel: +90 (242) 249 6975; Fax: +90 (242) 249 6903; E-mail: tbilgen@akdeniz.edu.tr doi:10.1111/j.1751-553X.2012.01456.x Received 15 March 2012; accepted for publication 13 June 2012 Keywords HBB, b-globin, 3′ UTR, mutation, intermedia SUMMARY Introduction: There are approximately 800 different genomic altera- tions of the b-globin gene described in the human hemoglobin var- iant (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 b-globin gene and describe their clinical implications. Methods: Four patients from two unrelated families, all with hemato- logical and clinical features associated with beta-thalassemia (b-thal), and their family members were included. The molecular diagnoses of the b-globin gene mutations were performed by direct sequencing. Results: A novel mutation, HBB:c.*+108 A>G, was found in combi- nation 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 HbA 2 levels. The other novel muta- tion, HBB:c.*+132 C>T, was found in combination with IVS-I- 1G>A (HBB:c.92 + 1G>A) in a 7-year-old boy diagnosed as b-thal intermedia from the second family. His father and two brothers were all carriers of HBB:c.*+132 C>T with borderline HbA 2 levels. Conclusion: Based on the observed b-thal intermedia phenotypes and the accompanying mutations, we conclude that these novel b-globin gene 3′ UTR mutations are associated with the mild phenotype of b-thal. INTRODUCTION Beta-thalassemia (b-thal) is a hereditary blood dis- order characterized by anomalies in the beta-chain synthesis of hemoglobin and displays a high level of molecular and clinical heterogeneity [1]. There are approximately 800 different genomic alterations related to the b-globin gene described in the human hemoglobin variant (HbVar) database [2]. The muta- tion type of the b-globin gene is a major determinant for the clinical severity of the disease [3]. Addition- ally, a number of other factors may contribute to the clinical variability seen in b-thal, and these range from nongenetic factors to additional genetic elements © 2012 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 1 ORIGINAL ARTICLE INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY International Journal of Laboratory Hematology The Official journal of the International Society for Laboratory Hematology