摘要
目的分析不稳定异常血红蛋白HbRush及其合并地中海贫血病例的血液学表型和基因型特征。方法对3例不明病因的贫血病例进行血液学常规检测和血红蛋白电泳，并检测α和β珠蛋白基因、^Gγ启动子区-158XmnI多态性位点和7个β珠蛋白基因簇中限制性酶切多态位点的单倍型。结果3例病例均具有小细胞低色素贫血表型，血红蛋白电泳HbF区域有定量值显著增高的异常条带（30．5％～59．2％），携带有不稳定血红蛋白Hb Rush突变（HBBCD101GAG〉CAG，Glu〉Gln），其中2例还携带有-α^3.7，CD17和HbE地中海贫血突变；HbRush突变有不同的β珠蛋白基因簇单倍型；未发现F区异常血红蛋白电泳条带与^Gγ启动子区多态和大片段β基因簇缺失的关联。结论本研究结果证实了中国不同人群中存在HbRush突变，是世界范围内第3个病例报告。HbRush异常血红蛋白可导致HbF区域电泳条带的定量值显著增高。单纯HbRush突变杂合子可产生小细胞低色素贫血及地中海贫血样临床症状，需进行产前诊断；对血红蛋白电泳HbF区域条带定量值明显增高的贫血病例及地中海贫血进行诊治时需考虑对HbRush的基因诊断和鉴别诊断。
Objective To analyze the hematological and genetic characteristics of unstable hemoglobin Rush （Hb Rush） and compound heterozygote of Hb Rush and thalassemia. Methods Peripheral blood samples and genomic DNA from three patients （including two ethnic Dai and one Han Chinese） with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 Xmn I polymorphic site of Gγ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing. Results All patients have presented hypochromic microcytic anemia and hemoglobin fraction with significant increased measurement （30.5%-59.2%） in the region of fetal hemoglobin during alkaline medium electrophoresis. DNA analysis suggested that all patients have carried mutations leading to the unstable hemoglobin Rush （HBB codon 101, GAG〉CAG, Glu〉Gln）. Two of them were compound heterozygotes of Hb Rush and thalassemia mutations of-α^3.7 ,CD17 and Hb E, respectively. Hb Rush mutation was associated with various haplotypes of the β-globin gene cluster. No significant association was found between increased abnormal hemoglobin fraction in the region of Hb F and the polymorphism of Gγ promoter or large deletion of the betaglobin gene cluster. Conclusion This study has confirmed the distribution of Hb Rush among various Chinese populations and is the third report of its kind. Hb Rush can result in increased measurement of hemoglobin fraction in the region of fetal hemoglobin （Hb F） during routine hemoglobin electrophoresis under alkaline condition. Hb Rush heterozygote alone can lead to hypochromic microcytic anemia and thalassemia-like phenotype. Prenatal diagnosis of Hb Rush is necessary for carriers.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2017年第1期15-20,共6页
Chinese Journal of Medical Genetics
基金
云南省应用基础重点研究项目（2013FA023）
国家高技术研究发展计划（863）项目（2012AA021802）
