Characterization of a novel HBB:c.194dup variant of the β-globin gene combined with six alpha genes

Abstract

β-thalassemia (β-thal) is one of the most prevalent inherited blood disorders in Ganzhou, south China. Next-generation sequencing was used to screen for thalassemia carriers in the general population. During the screening, we identified a novel β-thal variant in a 46-year-old Chinese man, which was validated by Sanger sequencing. Based on the patient’s clinical data, this novel mutation was classified as severe β0. However, the patient was mildly anemic (hemoglobin, 89 g/L), which was inconsistent with typical β0 carrier characteristics. On further evaluation, quantitative PCR indicated the presence of six α genes, while molecular analysis and pedigree analysis revealed the coexistence of αααanti3.7 and αααanti4.2. Therefore, we report a novel β-thal variant combined with six α genes. We describe the patient’s clinical phenotype and the process of molecular diagnosis. This case extends the spectrum of thalassemia variants.