A novel β-thalassemia variant at HBB:c.14delC (Codon 4, -C) identified via next-generation sequencing.

Objectives: β-Thalassemia (β-thal) is a genetic disease of the blood caused by mutations in the β-globin gene. Conventional methods for detecting thalassemia variants often miss rare and novel variants. Identifying the rare and novel β-thal variants, especially in the high prevalence regions, would enable better disease prevention.

Methods: A Chinese family who had joined the Thalassemia Prevention Program was recruited in this study. The β-thal carrier screening was performed using next-generation sequencing (NGS), and the results were validated through direct DNA sequencing. Hematological parameters were analyzed, and hemoglobin electrophoresis was performed. Additionally, the presence of thalassemia-associated deletions was determined using gap-polymerase chain reaction.

Results: A novel frameshift variant of β-thal, HBB:c.14delC(Codon 4, -C), was identified in a 31-year-old Chinese man. Subsequent genetic investigation showed that his mother also carried this novel variant. Hematological analysis and clinical evaluation suggested that this variant was present in the heterozygous state and might belong to a severe phenotype of β-thal.

Conclusions: We identified a novel frameshift variant of β-thal. NGS has the potential for identifying rare and novel thalassemia variants and broadening the spectrum of thalassemia screening and thus may contribute to effective prevention of thalassemia.