惠州地区客家人群罕见地中海贫血基因突变分析及产前诊断  

Analysis on rare thalassemia gene mutations among Hakka population in Huizhou region and prenatal diagnosis

作　　者：朱晓洁[1] 王鑫 刘丽洁 刘利敏[1] 余晓燕 蔡琳 吴显劲 ZHU Xiao-Jie;WANG Xin;LIU Li-Jie(Department of Laboratory Center,Huizhou Central People's Hospital,Huizhou,Guangdong 516001,China)

机构地区：[1]惠州市中心人民医院检验中心,广东惠州516001 [2]惠州市第三人民医院,广东惠州516003 [3]惠州市第二妇幼保健医院,广东惠州516004

出　　处：《中国妇幼保健》2019年第21期4987-4990,共4页Maternal and Child Health Care of China

基　　金：惠州市科技计划项目(2017Y009)

摘　　要：目的研究广东惠州地区客家人群罕见地中海贫血基因的突变类型及突变特点,干预中重型地贫儿的出生,为地贫的防控提供科学参考依据。方法收集2014年1月-2017年11月在惠州市中心人民医院进行地中海贫血筛查的客家人群样本2771例,筛选出符合条件的108例患者采集外周血进行血细胞分析及毛细管电泳血红蛋白分析,用导流杂交法进行常规α和β地中海贫血基因检测,采用多重链接探针扩增技术(MLPA)、DNA测序、缺口PCR(Gap-PCR)技术及血红蛋白持续增多症缺失型电泳等技术分析其罕见基因型。结果检测到62例罕见地贫基因突变,人群突变率约为2.24%(62/2771)。其中包含6种罕见的α珠蛋白基因突变,分别为泰国型(--THAI)、香港型(HKαα/αα)、两种α三联体(αααanti3.7、αααanti4.2)、CD74(GAC>CAC)以及CD30(-GAG);8种罕见β珠蛋白基因突变,分别为Vietnamese HPFH、Chinese Gγ+(Aγδβ)0、-90(C>T)、-31(A>G)、CD37 TGG>TAG、CD54-58(-TATGGGCAACCCT)、IVS-Ⅱ-2(-T)、及CD39(-A)。5对一方携带罕见地贫的同型地贫夫妇抽羊水进行了地贫产前诊断,检测到1例为中重型地贫儿,中重型地贫胎儿终止妊娠。结论本研究的数据充实了广东惠州地区客家人群的地贫基因突变图谱。当血液学表型与基因型不符时,在排除缺铁性贫血后应进一步做罕见基因型的检测以避免漏诊或误诊,特别是生育过重型地贫患儿的夫妇。这有助于指导临床诊断、人群筛查和遗传咨询。Objective To research rare thalassemia gene mutation types and characteristics among Hakka population in Huizhou region of Guangdong,prevent the birth of neonates with moderate and severe thalassemia,provide a reference basis for prevention and control of thalassemia.Methods A total of 2771 Hakka women undergoing thalassemia screening in Huizhou Central People's Hospital from January 2014 to November 2017 were collected,then 108 patients meeting the inculsion criteria were screened out,peripheral blood samples were collected to conduct whole blood cell analysis and hemoglobin analysis with capillary zone electrophoresis.Flow-through hybridization was used to detect conventionalαandβthalassemia genes.Multi-link probe amplification technology(MLPA),DNA sequencing,gap PCR(Gap-PCR),and hemoglobin electrophoresis were used to analyze the rare genotypes.Results Sixty-two ceses were diagnosed as rare thalassemia gene mutations,the population gene mutation rate was 2.24%(62/2771),including 6 rareα-globin gene mutations[-THAI,HKαα,αααanti3.7,αααanti4.2,CD74,CD30(-GAG)]and 8 rareβ-globin gene mutations[Vietnamese HPFH,Chinese Gγ+(Aγδβ)0,-90(C>T),-31(A>G),CD37 TGG>TAG,CD54-58(-TATGGGCAACCCT),IVS-Ⅱ-2(-T),CD39(-A)].Five couples with the same type of thalassemia underwent prenatal diagnosis of thalassemia of amniotic fluid,one fetus was diagnosed as moderate and severe thalassemia,pregnancy was terminated.Conclusion The data of present study enrich gene mutation spectrum of rare thalassemia among Hakka population of Huizhou region in Guangdong.After excluding iron deficiency anemia,when the results of hematological phenotype and genotype do not match,further detection of rare genotypes should be conducted to avoid missed diagnosis or misdiagnosis,especially the couples with children with severe thalassemia.The finding can direct clinical diagnosis,population screening,and genetic counseling.

关 键 词：罕见基因型 地中海贫血 产前诊断 客家人群 

分 类 号：R55[医药卫生—血液循环系统疾病]