Mutational spectrum of HBD gene in the Chinese population: Description of 36 mutations including 11 novel variants

Abstract

Introduction: Mutations in the hemoglobin subunit delta (HBD) gene (MIM#142000) are associated with decreased levels of the Hemoglobin A₂ (Hb A₂ ) fraction. We aimed to examine the prevalence of HBD gene mutations and summarize their characteristics in the Chinese population.

Methods: Individuals who exhibited Hb A₂ levels below 1.8%, with or without Hb A₂ variant peaks, were chosen for further investigation. Hemoglobin analysis was conducted using capillary electrophoresis. Common α and β-thalassemia in China were detected using gap-PCR and reverse dot blot hybridization. The presence of HBD gene mutations was confirmed by DNA sequencing.

Results: A total of 188 patients were identified as carriers of the HBD gene mutation, with a prevalence of approximately 0.46%. We discovered 36 types of mutations, 30 of which resulted in δ-globin variants, while the remaining 6 resulted in δ-thalassemia. The most common mutation was HBD:c.-127 T > C, accounting for 87.2% of δ-thalassemia cases. In addition, we identified 11 novel HBD gene mutations and found 10 cases compounded with other common thalassemias.

Conclusion: We observed a high prevalence of HBD gene mutations in southern China. Our findings provide a genetic basis for screening for δ-thalassemia and enrich the spectrum of HBD gene mutations.

Keywords: Chinese population; HBD gene mutation; Hb A2; hemoglobin variant; thalassemia.