Two novel mutations in the 3′ untranslated region of the beta‐globin gene that are associated with the mild phenotype of beta thalassemia

Summary Introduction There are approximately 800 different genomic alterations of the β‐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 β‐globin gene and describe their clinical implications. Methods Four patients from two unrelated families, all with hematological and clinical features associated with beta‐thalassemia (β‐thal), and their family members were included. The molecular diagnoses of the β‐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 HbA 2 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 β‐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 β‐thal intermedia phenotypes and the accompanying mutations, we conclude that these novel β‐globin gene 3′ UTR mutations are associated with the mild phenotype of β‐thal.