β-珠蛋白基因IVS-Ⅱ-1(G>A)突变纯合子的基因型及表型分析  

The genotype and phenotype analysis of a rare mutation IVS-Ⅱ-1(G>A)onβ-globin gene

作　　者：郭莹莹 林伟雄 肖璇 陈萍 Guo Yingying;Lin Weixiong;Xiao Xuan;Chen Ping(Guangxi Collaborative Innovation Center for Biomedicine;Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment;Key Laboratory of Thalassemia Medicine,Chinese Academy of Medical Sciences;Guangxi Key laboratory of Thalassemia Research,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西生物医药协同创新中心 [2]广西—东盟重大疾病防治协同创新中心 [3]中国医学科学院地中海贫血防治研究重点实验室 [4]广西地中海贫血防治重点实验室,南宁530021

出　　处：《广西医科大学学报》2021年第5期1009-1012,共4页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81960574);中国医学科学院中央级公益性科研院所项目(No.2018PT32020);广西地中海贫血防治临床医学研究中心建设项目(No.AD17129061;No.2018-15-Y01)。

摘　　要：目的:对β-珠蛋白基因内含子突变的基因型及其表型进行分析。方法:选取广西医科大学第一附属医院2019年7月至2020年9月收治及进行地中海贫血检测的病例,应用血细胞分析仪进行血常规检测;血红蛋白分析仪进行血红蛋白定量分析;Gap-PCR及荧光PCR熔解曲线法等检测常见β-地中海贫血和α-地中海贫血基因突变类型;DNA测序检测罕见β-地中海贫血基因突变类型。结果:共检出401例β-地中海贫血病例,其中1例为罕见β-珠蛋白基因IVS-Ⅱ-1(G>A)纯合子突变。病例为男性,2岁6个月,有输血史,有肝脾肿大。血常规分析显示:血红蛋白(Hb)66.5 g/L、红细胞(RBC)2.83×1012/L、平均红细胞体积(MCV)72.06 fL、平均红细胞血红蛋白(MCH)23.52 pg、红细胞平均血红蛋白浓度(MCHC)326.4 g/L和红细胞比容(HCT)0.204 L/L。血红蛋白分析结果显示,Hb A24.7%,Hb F 91.5%。基因分析及DNA测序结果显示β-珠蛋白基因IVS-Ⅱ-1(G>A)纯合子突变。结论:首次在国内检出β-珠蛋白基因IVS-Ⅱ-1(G>A)突变纯合子,临床表现为中度贫血,血红蛋白分析提示Hb F水平明显升高。此类型基因突变在国内较为罕见,临床上容易漏诊。Objective:To analyze the genotype and phenotype ofβ-globin intron gene mutation.Methods:Cases were collected in the First Affiliated Hospital of Guangxi Medical University from July 2019 to September 2020.Blood routine test was performed with automatic blood cell analyzer.Hb analysis was conductedby hemoglobin(Hb)analyzer.Gap-PCR and fluorescence PCR melting curve analysis were used to detect common mutations ofα-thalassemia andβ-thalassemia.The rare mutations were detected by DNA sequencing.Results:A total of 401 cases withβ-thalassemia were collected in this study.Among them,one case was detected to be the mutation of IVS-II-1(G>A)onβ-globin gene.The case was a boy,two and a half years old,who had hepatosplenomegaly and the history of blood transfusion.Blood routine test showed that Hb 66.5 g/L,RBC 2.83×1012/L,MCV 72.06 fL,MCH 23.52 pg,MCHC 326.4 g/L and HCT 0.204 L/L respectively.The result of hemoglobin analysis showed that Hb A2 was 4.7%and Hb F was 91.5%.DNA sequencing detected the homozygous mutation of IVS-II-1(G>A)onβ-globin gene.Conclusion:Homozygous mutation of IVS-II-1(G>A)onβ-globin gene was found for the first time in Guangxi province.The case had moderate anemia.Hb analysis showed thatthe level of Hb F was significantly elevated.This mutation isrelatively rare in Chinese and easy to be misdiagnosed in clinical practice.

关 键 词：Β-地中海贫血 Β-珠蛋白基因 IVS-Ⅱ-I(G>A)突变 临床表型 

分 类 号：R556.61[医药卫生—血液循环系统疾病]