Analysis of genotypic distribution and rare variants of patients with α/β-thalassemia screened in one hospital in Beijing, China

Thalassemia is among the most common inherited diseases worldwide. We aimed to analyze the genotype and frequency distribution of thalassemia in a general hospital in Beijing and provide a reference for genetic counseling and prenatal diagnosis. A total of 3196 cases of thalassemia screened at Peking Union Medical College Hospital (PUMCH) between January 2018 and January 2022 were collected. Thalassemia genotypes were tested using gap polymerase chain reaction (gap-PCR), PCR, reverse dot blot (RDB), and Sanger sequencing analyses. The pathogenicity of the rare variants was analyzed using bioinformatics approaches. Total of 1936 positive routine α/β-thalassemia were detected from 3196 blood samples, including 733 α-thalassemia variants, 1170 β-thalassemia variants, and 33 cases with concurrent α- and β-thalassemia variants. Two novel variants, HBA2:c.300+82G>C and HBB:codon85(-T), were identified in HBA2 and HBB genes, respectively, and were not detected in the ExAC, gnomAD, HbVar, and HGMD databases. The genotype distribution of thalassemia in a general hospital in Beijing is complex and heterogeneous. The novel variants in HBA2 and HBB are likely to underlie α/β-thalassemia in these patients.