Large‐Scale Analysis of the Thalassemia Mutation Spectrum in Guizhou Province, Southern China, Using Third‐Generation Sequencing

ABSTRACT This study aimed to comprehensively characterize the molecular spectrum of thalassemia by retrospectively analyzing genetic screening results from a large cohort of individuals. Peripheral blood samples were collected from 26 047 individuals seeking care at the Departments of Obstetrics and Gynecology, Pediatrics, Reproductive Medicine, and Hematology across multiple regional hospitals in Guizhou Province, China. Thalassemia gene mutations were analyzed using targeted third‐generation sequencing (TGS) to assess the mutation spectrum in this population. Of the cohort, 5099 individuals were identified as thalassemia carriers, yielding an overall carrier rate of 19.58%. The carrier rates differed significantly between the southern and northern regions of Guizhou ( p < 0.001). α‐thalassemia included 40 distinct genotypes, β‐thalassemia comprised 33 genotypes, and cases with concurrent α‐ and β‐thalassemia mutations exhibited 47 unique genotypes. A total of 17 distinct mutations were identified in the α‐thalassemia gene and 26 in the β‐thalassemia gene. The mutation spectrum in Guizhou showed significant differences when compared to other southern Chinese populations, with notable regional variations within Guizhou itself. This study highlights the substantial genetic diversity and distinct mutation patterns of thalassemia in Guizhou Province. These findings provide valuable insights into the distribution of thalassemia genotypes and alleles, which can inform genetic counseling and prenatal screening strategies tailored to this population.