A Decade‑Long Genetic Epidemiological Profile of Thalassemia in the Childbearing‑Age Population of Huizhou, a Major Hakka Center in Guangdong, China

Le résumé fourni par la source

This retrospective study established the first comprehensive genetic epidemiological profile of thalassemia in the childbearing‑age population (n = 343,580) of Huizhou, a major Hakka center in Guangdong, China, over a decade (2015–2024). The overall carrier rate was 12.23%, comprising 8.04% α‑thalassemia, 3.58% β‑thalassemia, and 0.60% concurrent α‑ and β‑thalassemia. The α‑thalassemia spectrum was dominated by the --SEA deletion (71.11%), while the β‑thalassemia profile featured a distinctive local signature with significantly elevated frequencies of β‑28 (A > G), βCD41‑42, and βIVS‑II‑654. HbH disease was identified in 698 individuals (0.20%), with genotypes --SEA/-α3.7 (428), --SEA/-α4.2 (146), --SEA/αWSα (98), and --SEA/αCSα (26). Rare variants included SEA‑HPFH (162, 0.047%) and Chinese Gγ+(Aγδβ) 0 δβ‑thalassemia (145, 0.042%); co‑inheritance with β‑thalassemia occurred in 2.47% of SEA‑HPFH carriers and 1.38% of δβ‑thalassemia carriers. Hematological characterization across common genotypes revealed a clear severity gradient: --SEA/αα carriers exhibited the most marked microcytic hypochromia, while αWSα/αα and βCD26/βN (HbE) carriers showed the mildest phenotypes, highlighting inter‑genotypic heterogeneity with direct implications for genetic counseling. Geographic analysis revealed widespread core genotypes alongside spatially clustered rare alleles. Based on these integrated molecular and hematological findings, we propose a pragmatic two‑tiered prevention strategy: primary high‑throughput screening focused on five core genotypes, followed by mandatory reflex comprehensive genotyping for high‑risk subgroups and a dedicated diagnostic pathway for complex cases, tailored to enhance diagnostic accuracy and reduce severe thalassemia incidence in this region.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.