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

Abstract

Hemoglobinopathies are caused by genetic defects on the globin genes. To date, more than 900 β-globin variants have been recorded worldwide. These gene alterations often cause either a decrease in β-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 β variant, Hb Zunyi [β147(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 β-globin gene, and leads to severe thalassemia. In patient 2, we discovered the rare Hb Southampton mutation [β106(G8)Leu→Pro; HBB: c.320T>C], while in patient 3, the rare Hb Alesha mutation [β67(E11)Val→Met (GTG>ATG); HBB: c.202G>A] was detected. The identification of the novel β variant, Hb Zunyi, has added to the human globin database and will shed light on future diagnosis of hemoglobinopathy/thalassemia and genetic counseling.

Keywords:

• β-Globin gene
• β-thalassemia (β-thal)
• hemoglobinopathy
• mutation

Acknowledgements

We thank the three patients and their parents for their willingness to share their stories.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by Department of Science and Technology in Guihou Grant No. [2019]2806.