α2珠蛋白基因起始密码子突变导致α-地中海贫血的研究  

INITIATION CODON MUTATION OF α2-GLOBIN GENE CAUSING α-THALASSEMIA

作　　者：高清丽[1] 张学[1] 陈萍[1] 李树全[1] 丘玉玲 肖旋[1] 杨得寨 

机构地区：[1]广西医科大学第一附属医院血红蛋白研究室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》2016年第2期266-269,共4页Journal of Guangxi Medical University

基　　金：卫生和计划生育委员会卫生行业科研专项(No.201202017);科技部科技支撑计划(No.2012BAI09B01);广西科学研究与技术开发计划项目(No.桂科合0992032-11);广西壮族自治区人口和计划生育委员会科研基金资助项目(No.1108)

摘　　要：目的:分析血红蛋白H病(hemoglobin H disease,Hb H病)的基因型与临床特征。方法:对2015年4月至2015年12月在广西医科大学第一附属医院经血常规、血红蛋白分析确诊为Hb H病的200例患者,利用聚合酶链式反应(PCR)、反向斑点杂交(RDB)及DNA测序等方法进行α-地中海贫血基因突变分析。结果:在200例Hb H病患者中发现1例罕见的Hb H病。病例为男性,30岁,无黄疸、肝脾肿大等,未输过血。血常规结果显示:Hb 87g/L,RBC 4.57×1012 L,MCV 67.7fL,MCH 19pg,HCT 0.285。血红蛋白分析示:Hb H+Hb Bart′s 26.6%,Hb A21.5%,Hb F 0.7%,基因分析结果为α2珠蛋白起始密码子突变(ATG→A-G)复合东南亚缺失型α-地中海贫血-1(--SEA/αATG→A-Gα)。病例的家系调查提示其父亲血常规和血红蛋白分析正常,基因分析为α2珠蛋白起始密码子突变(ATG→A-G)杂合子(αATG→A-Gα/αα);其母亲血常规检测结果:Hb 111g/L,RBC 4.9×1012 L,MCV 69.4fL,MCH 22.6pg,MCHC 326g/L,HCT 0.341,基因分析为东南亚缺失型α-地中海贫血(--SEA/αα)。结论:这是中国人群中首次发现α2珠蛋白起始密码子突变导致α-地中海贫血。其杂合子无临床症状,血液学检测正常,Hb分析正常。当复合东南亚缺失型α-地中海贫血-1时导致Hb H病,临床有轻度贫血。此基因突变类型容易漏诊,需基因分析才能确诊。Objective：To analyze the genotype and clinical phenotype of Hemoglobin H（Hb H）disease.Methods：From April 2015 to December 2015,200 cases diagnosed as Hb H disease by hemalogic and hemoglobin analysis at The First Affiliated Hospital of Guangxi Medical Univeristy,were recruited in this study.Thalassemia mutations were analyzed by gap-polymerase chain reaction（gap-PCR）,reverse dot blot hybridization（RDB）and DNA sequencing.Results：An uncommon case with Hb H disease was found among the 200 cases.This case was a 30 years old male,who had no jaundice,no hepatosplenomegaly,and no history of blood transfusion.His hematological data showed Hb 87g/L,RBC 4.57×1012 L,MCV 67.7fL,MCH 19 pg,MCHC 304.4g/L and HCT 0.285.Hemoglobin analysis showed Hb H＋Hb Bart′s 26.6%,Hb A21.5%,and Hb F 0.7%.DNA sequencing confirmed an initation codon mutation（ATG→A-G）onα2-globin gene and combined with SEAα-Thalassemia-1mutation.Family survey suggested that his father,whose blood routine test and Hb analysis were normal.DNA sequencing showed that his father was a heterozygote for the initation codon mutation（ATG→A-G）onα2-globin gene.The mother was heterozygote of SEAα-Thalassemia-1（--SEA/αα）,with Hb 111g/L,RBC 4.9×1012 L,MCV 69.4fL,MCH 22.6pg,MCHC 326g/L and HCT 0.341.Conclusion：This is the first report that initiation codon mutation ofα2-globin gene causes α-Thalassemia in Chinese.The heterozygote has no clinical symptoms with normal hematologic parameters and Hb analyses.When initiation codon mutation ofα2-globin co-inherits with SEAα-Thalassemia-1,may lead to Hb H disease with mild anemia.This initation codon mutation is easily to be missed,and only can be confirmed by DNA sequencing.

关 键 词：Α-地中海贫血 HB H病 起始密码子突变 基因型 临床特征 

分 类 号：R556.9[医药卫生—血液循环系统疾病]