Severe Thalassemia Caused by Hb Zunyi [β147(HC3)Stop→Gln; HBB: c.442T>C)] on the β-Globin Gene

Hemoglobinopathies are caused by genetic defects on the globin genes. To date, more than 900 beta-globin variants have been recorded worldwide. These gene alterations often cause either a decrease in beta-globin synthesis or completely block synthesis, leading to a hemoglobinopathy. While most of these causative mutations are inherited, de novo mutations are quite rare. Here, we investigated three hemoglobinopathy cases. These patients developed severe hemolytic anemia at 3-5 months of age and were transfusion-dependent. In patient 1, a novel beta variant, Hb Zunyi [beta 147(HC3)Stop -> Gln; HBB: c.442T>C] was identified. This de novo mutation results in a stop codon substitution to a glutamine residue at codon 147 of the beta-globin gene, and leads to severe thalassemia. In patient 2, we discovered the rare Hb Southampton mutation [beta 106(G8)Leu -> Pro; HBB: c.320T>C], while in patient 3, the rare Hb Alesha mutation [beta 67(E11)Val -> Met (GTG>ATG); HBB: c.202G>A] was detected. The identification of the novel beta variant, Hb Zunyi, has added to the human globin database and will shed light on future diagnosis of hemoglobinopathy/thalassemia and genetic counseling.