High prevalence of Hb Q-Thailand not in cis with the -α4.2 deletion: genotypes, phenotypes, and implications in the cenxi population of southern China

Objectives Hb Q-Thailand, a common hemoglobin variation in Southeast Asia, has historically been associated with the -α 4.2 deletion. However, in the Cenxi population of southern China, this variant is frequently detected without the -α 4.2 deletion. This study aimed to investigate the carrier rate, genotype distribution, and phenotypic characteristics of Hb Q-Thailand not associated with the -α 4.2 deletion in this population. Methods A total of 23,546 individuals who underwent capillary electrophoresis screening at our hospital between January 2024 and December 2025 were enrolled in this study. Deletional α-thalassemia mutations were detected using Gap-PCR, while common α-globin chain mutations were identified by PCR-reverse dot blot hybridization (PCR-RDB). Additionally, 17 common β-thalassemia point mutations were analyzed using PCR-RDB. Sanger sequencing was performed to characterize α-globin variants. Results Thirty-seven positive cases were identified among the 23,546 screened individuals, yielding a positive screening rate of 0.16% (37/23,546) in the Cenxi population. Genetic confirmation was performed in 22 cases, of which 21 were confirmed to carry Hb Q-Thailand, while the remaining case was identified as a rare variant, Hb Zhaoqing. Notably, 10 samples exhibited Hb Q-Thailand without linkage to the -α 4.2 deletion, accounting for a substantial proportion of 47.6% (10/21) among confirmed cases. In the group with Hb Q-Thailand not linked to the -α 4.2 deletion, hematological phenotypes were largely within normal ranges. The Hb Q-Thailand level in simple heterozygotes was 16.6% ± 0.4%, which increased to 22.4% ± 0.4% when co-inherited with the -α 3.7 deletion. In contrast, the majority of individuals in the group with Hb Q-Thailand linked to the -α 4.2 deletion exhibited abnormal hematological parameters. The Hb Q-Thailand level in this group was 28.2% ± 0.8%, rising to 42.0% when the -α 3.7 deletion was co-inherited. Additionally, one case in this group was found to co-inherit β-thalassemia trait, presenting with hematological and electrophoretic features consistent with β-thalassemia trait, characterized by elevated Hb A 2 and reduced MCV/MCH. Conclusion The Cenxi population presents a high proportion of Hb Q-Thailand cases in which the variant is not linked to the -α 4.2 deletion. Hematological phenotypes differ significantly depending on the presence or absence of linkage to the -α 4.2 deletion.