Genotypic distribution and molecular spectrum of rare and novel thalassemia variants in Ganzhou, southern China

Background Thalassemia is the most common single-gene inherited blood disorder worldwide, being relatively rare in northern China but more prevalent in southern China. To facilitate effective prevention and control of thalassemia, we analyze the genotype and frequency distribution of rare thalassemia variants in the general population of the Ganzhou area, offering valuable insights for genetic counseling and prenatal diagnosis. Methods Between January 2022 and January 2025, a cohort of 84,067 individuals was screened in Ganzhou. Following the exclusion criteria, 1,081 participants with rare thalassemia variants were included in the final analysis. Genotypes associated with thalassemia were determined using next-generation sequencing (NGS). Variant classification adhered to ACMG/AMP guidelines. Results Among the participants with rare thalassemia variants, 495 individuals presented with rare α-thalassemia variants and 560 with rare β-thalassemia variants, including 26 newly identified variants. Rare thalassemia variants accounted for 1.29% of the total screened population. The distribution of rare thalassemia variants exhibited regional variation across Ganzhou, with the highest rates in Nan Kang (12.69%), followed by Xingguo (10.49%) and Zhanggong (8.80%). Chongyi had the lowest rate at 1.78%, with all these locations located to the northwest of Ganzhou. Additionally, 26 individuals carried novel thalassemia variants. Six of these variants were classified as “Likely Pathogenic,” and the HBB:c.50G>T (Gly > Val) genotype was associated with hypochromic anemia. Conclusion This study offers a comprehensive analysis of rare and newly identified thalassemia variants in the Ganzhou area, highlighting the complexity and heterogeneity of the condition. These findings underscore the necessity for effective screening methods in regions with a high incidence of thalassemia and provide essential insights for the targeted prevention and management of this disorder in the future.