First clinical and pedigree study of rare HBB: c.316-90 A > G variant in β-globin gene in Chinese population using third-generation sequencing

Introduction: β-thalassemia is a common genetic disease mainly caused by point mutations in the β-globin gene, eliciting a high prevalence in South China. The aim of the present study is to identify a rare HBB: c.316-90 A > G variant and provide the clinical and hematological features in two unrelated Chinese families.

Methods: In this study, we collected eight subjects from two unrelated Chinese families. Conventional thalassemia gene testing was performed to investigate common α and β-thalassemia variants based on the PCR reverse dot hybridization technique. Third-generation sequencing (TGS) was utilized to examine the rare or novel HBA1, HBA2 and HBB gene variants, which will be further verified using Sanger sequencing.

Results: A rare HBB: c.316-90 A > G variant was identified in the proband of Family 1 using TGS, and exhibited remarkably low levels of hemoglobin (Hb), Hb A2, MCV and MCH. The other members in Family 1 did not have the HBB: c.316-90 A > G variant and elicited normal hematological screening results. In Family 2, the proband also carried the HBB: c.316-90 A > G variant and exhibited low levels of MCV, MCH and Hb A2, but with normal Hb value. However, pedigree analysis results revealed that the proband's mother and nephew also carried the HBB: c.316-90 A > G variant, but with normal hematological screening results.

Conclusion: This study first conducts clinical and hematological analysis of the HBB: c.316-90 A > G variant in two unrelated Chinese families, which provides valuable data for genetic counseling of the corresponding individuals.