湘潭市产前人群δ珠蛋白基因突变谱及表型分析

Mutation spectrum and phenotype analysis of hemoglobin subunit delta gene among prenatal population in Xiangtan City

目的分析湘潭市产前人群δ珠蛋白(hemoglobin subunit delta,HBD)基因突变谱及血液学表型,为罕见、复杂血红蛋白病的筛查和诊断提供科学依据。方法选取2022年10月至2023年12月在湘潭市妇幼保健院进行地中海贫血(简称地贫)筛查和基因检测的产前人群为研究对象,结合毛细管电泳结果进一步进行HBD基因测序,鉴定具体基因型。结果共纳入5371例受试对象,检出HBD基因突变22例,突变携带率为0.41%(22/5371)。其中,14例为δ地贫、7例为δ异常血红蛋白、1例为δ地贫合并δ异常血红蛋白;共包括7种HBD突变基因型,以-77(T>C)最为常见,其次是血红蛋白(Hb)A 2-Huadu和CD34(+GGT),分别占68.2%(15/22)、9.1%(2/22)、9.1%(2/22)。CD34(+GGT)为新发现基因型,CD7(GAG>TAG)为中国人群中首次报道。22例HBD基因突变携带者Hb含量、平均红细胞体积、平均红细胞血红蛋白含量均正常或接近正常;毛细管电泳均表现为Hb A 2含量降低。结论湘潭市产前人群有HBD基因突变检出,-77(T>C)是最常见的突变基因型;突变携带者均无贫血表现。

Objective To analyze the mutation spectrum and hematological phenotype of hemoglobin subunit delta(HBD)gene among prenatal population in Xiangtan City,and to provide scientific basis for screening and diagnosis of rare and complex hemoglobinopathia.Methods Prenatal population underwent screening and genetic testing for thalassemia at Xiangtan Maternal and Child Health Hospital from October 2022 to December 2023 were selected as the study subjects,combined with capillary electrophoresis results,further HBD gene sequencing was performed to identify specific genotypes.Results A total of 5371 subjects were enrolled,22 cases of HBD gene mutations were detected,with a mutation carrier rate of 0.41%(22/5371).Among them,14 cases were diagnosed withδthalassemia,7 cases wereδabnormal hemoglobin,and 1 case wasδthalassemia combined withδabnormal hemoglobin.There were 7 HBD mutant genotypes were included,with-77(T>C)being the most common,followed by hemoglobin(Hb)A 2-Huadu and CD34(+GGT);accounting for 68.2%(15/22),9.1%(2/22),9.1%(2/22).CD34(+GGT)was a newly discovered genotype,and CD7(GAG>TAG)was the first reported genotype in Chinese population.The Hb content,mean corpuscular volume,and mean corpuscular hemoglobin content were normal or nearly normal in 22 carriers of the HBD gene mutation;capillary electrophoresis demonstrated reduced Hb A 2 content in all cases.Conclusions HBD gene mutations have been detected in the prenatal population in Xiangtan City,with-77(T>C)being the most common mutation genotype.None of the mutation carriers showed anemia.