Molecular Epidemiology of δβ-Thalassemia and Hereditary Persistence of Fetal Hemoglobin (HPFH) in the Quanzhou Childbearing-Age Population, China.

Abstract

δβ-Thalassemia and hereditary persistence of fetal hemoglobin (HPFH) are uncommon hemoglobinopathies. This study aimed to define the molecular epidemiological features of δβ-thalassemia and HPFH in the childbearing-age population of Quanzhou, China, to inform precise prevention strategies and genetic counseling. From a free pre-pregnancy thalassemia screening cohort (n = 19,154), 92 individuals with elevated HbF (≥2%) and 11 control groups with normal HbF (≤2%) were included. DNA analysis of common deletion-type δβ-thalassemia/HPFH mutations (SEA-HPFH, Chinese type Gγ+(Aγδβ)⁰, Taiwan type β⁰) and non-deletion-type HPFH mutations was performed by gap-PCR, PCR-reverse dot hybridization, and Sanger sequencing. The correlation between hematological parameters and genotypes was also analyzed. The results suggest that the detection rate of deletion-type HPFH/δβ-thalassemia was 0.063% (12/19154), mainly SEA-HPFH and Chinese Gγ+(Aγδβ)⁰. The detection rate of γ-globin gene mutations and non-deletion-type HPFH was 0.329% (63/19154). 9 different γ-globin promoter mutations were identified. The most frequently detected variants were HBG2:c.-211C>T, HBG1:c.-29G>A, and HBG1:c.-272_-275dupAGCA. However, based on functional relevance, three key variants were highlighted: HBG1:c.-211C>T, HBG1:c.-249C>T, and the novel HBG2:c.-253_-254dup. The remaining variants (HBG1:c.-29G>A, HBG1:c.-272_-275dupAGCA, HBG1:c.-404A>G, HBG1:c.-417G>C, HBG1:c.-420C>A) are described as benign polymorphisms or variants in strong linkage disequilibrium with HBG2:c.-211C>T. Deletion-type δβ-thalassemia/HPFH is rare in Quanzhou. SEA-HPFH and Chinese Gγ+(Aγδβ)⁰ are more common. Non-deletion-type HPFH, especially the double heterozygous state HBG1:c.-29G>A/HBG2:c.-211C>T, is significantly more common. These findings reveal the unique molecular epidemiological characteristics of δβ-thalassemia and HPFH in this region, providing important data for genetic counseling and prenatal diagnosis.