常见δβ地中海贫血/HPFH的分子流行病学特征及鉴别诊断  

Molecular Epidemiological Characteristics and Differential Diagnosis of Commonδβ⁃Thalassemia/HPFH

作　　者：鞠爱萍[1] 李娜 林铿[1] 黄慧慧[1] 刘淑贤[1] 江帆 JU Ai-Ping;LI Na;LIN Keng;HUANG Hui-Hui;LIU Shu-Xian;JIANG Fan(Department of Laboratory Medicine,Maternity and Child Health Hospital of Huadu District,Guangzhou 510800,Guangdong Province,China;The Tanbu Town Central Hospital of Huadu District,Guangzhou 510820,Guangdong Province,China;Guangzhou Women and Children′s Medical Center,Guangzhou 510620,Guangdong Province,China)

机构地区：[1]广州市花都区妇幼保健院检验科,广东广州510800 [2]广州市花都区炭步镇中心医院,广东广州510820 [3]广州市妇女儿童医疗中心,广东广州510620

出　　处：《中国实验血液学杂志》2022年第4期1182-1187,共6页Journal of Experimental Hematology

基　　金：广州市花都区医疗卫生一般科研专项项目(21⁃HDWS⁃108)。

摘　　要：目的:探讨广州市花都地区育龄人群中常见δβ地中海贫血/遗传性胎儿血红蛋白持续存在综合征(HPFH)的分子流行病学特征,为地中海贫血防控提供实验室依据。方法:收集2016年1月至2021年7月参加免费地中海贫血检测的广州花都区育龄人群血液样本,进行血常规及血红蛋白电泳检测,对HbF≥5%样本且测序未见异常样本采用Gap⁃PCR(Gap⁃Polymerase Chain Reaction)检测中国型Gγ+(Aγδβ)0地中海贫血、东南亚型HPFH(SEA⁃HPFH)、台湾型β地中海贫血;HbF≥5%样本中针对HBG1、HBG2启动子近端设计引物,利用Sanger测序检测启动子区近端的点突变,并对其血液学参数进行统计分析。结果:27088例受检者中检出中国型Gγ+(Aγδβ)0地中海贫血13例,其中复合⁃⁃^(SEA)/αα3例,1例β⁃28(A>G)/βChinese Gγ+(Aγδβ)0;检出SEA⁃HPFH 33例,复合⁃⁃^(SEA)/αα3例;6例Aγ⁃196 C>T导致的非缺失型HPFH;未检出台湾型地中海贫血基因型。常见缺失型/非缺失型β地中海贫血总检出率为0.19%(52/27088),中国型Gγ+(Aγδβ)0地中海贫血、SEA⁃HPFH、Aγ⁃196 C>T组血液学参数平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)、血红蛋白A_(2)(HbA_(2))、血红蛋白F(HbF)水平具有统计学差异(P<0.001);Aγ⁃196 C>T合并α0地贫样本血液学参数与中国型Gγ+(Aγδβ)0/βN地中海贫血类似,仅HbA_(2)明显低于后者,有助于临床鉴别。结论:花都区育龄人群δβ地中海贫血/HPFH需纳入地贫防控监测范围,血液学参数可为鉴别不同类型δβ地中海贫血/HPFH提供部分依据。Objective:To investigate the molecular epidemiological characteristics of commonδβ⁃thalassemia/hereditary persistence of fetal hemoglobin(HPFH)in the prepregnant population in Huadu,and to provide a laboratory basis for prevention and control of thalassemia.Methods:Blood samples of childbearing age people in Huadu District of Guangzhou who participated in free thalassemia testing from January 2016 to July 2021 were collected for hematological parameters analysis and hemoglobin electrophoresis.Chinese Gγ+(Aγδβ)0⁃thalassemia,SEA⁃HPFH and Taiwan Residents deletionβ⁃thalassemia were detected by Gap⁃PCR in the samples with higher HbF(≥5%).Primers were designed for the proximal HBG1 and HBG2 promoter,and the point mutations in the proximal promoter region were detected by Sanger sequencing.Hematology parameters data were statistically analyzed.Results:Among 27088 samples,Thirteen cases of Chinese Gγ+(Aγδβ)0⁃thalassemia and thirty⁃three cases of SEA⁃HPFH were detected,which including 3 cases of Chinese Gγ+(Aγδβ)0/βN compounded with⁃⁃SEA/ααand three cases of SEA⁃HPFH/βN compounded with⁃⁃SEA/αα.6 carriers with Aγ⁃196 C>T were also detected;No Taiwan Residents thalassemia genetype was detected.The total detection rate of commonδβ⁃thalassemia/HPFH was 0.19%(52/27088).There were significant differences in the levels of MCV,MCH,HbA2,and HbF among Chinese Gγ+(Aγδβ)0⁃thalassemia,SEA⁃HPFH,Aγ⁃196 C>T(P<0.001).The hematological parameters of Aγ⁃196C>T combined withα0⁃thalassemia were similar to those of Chinese Gγ+(Aγδβ)0⁃thalassemia carriers,and only HbA2 was significantly lower than that of the latter,which was helpful for clinical identification.Conclusion:δβ⁃thalassemia/HPFH should be included in the scope of thalassemia prevention program in the prepregnant population in Huadu District,and hematological parameters can provide some basis for identifying different types ofδβ⁃thalassemia/HPFH.

关 键 词：常见δβ地中海贫血/HPFH 分子流行病学 鉴别诊断 

分 类 号：R556.61[医药卫生—血液循环系统疾病]