^(A)γ-珠蛋白基因启动子区域-114~-102缺失突变导致非缺失型遗传性持续性胎儿血红蛋白综合征的研究  

Study on the deletion mutation in the promoter region-114 to-102 of ^(A)γ-globin gene inducing non-deletional hereditary persistence of fetal hemoglobin

作　　者：罗丹 柴子萱 肖璇 朱恒莹 陈萍 LUO Dan;CHAI Zixuan;XIAO Xuan;ZHU Hengying;CHEN Ping(Life Sciences Institute,Guangxi Medical University,Nanning 530021,China;NHC Key Laboratory of Thalassemia Medicine,Nanning 530021,China;Key Laboratory of Thalassemia Medicine,Chinese Academy of Medical Sciences,Nanning 530021,China;Guangxi Key Laboratory of Thalassemia Research,Nanning 530021,China)

机构地区：[1]广西医科大学生命科学研究院,南宁530021 [2]国家卫生健康委地中海贫血防治重点实验室,南宁530021 [3]中国医学科学院地中海贫血防治研究重点实验室,南宁530021 [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》2024年第6期905-909,共5页Journal of Guangxi Medical University

基　　金：广西科技计划项目(No.桂科AD23026025);国家自然科学基金资助项目(No.81960574)。

摘　　要：目的:研究^(A)γ-珠蛋白基因启动子区域-114~-102缺失突变病例的基因突变特点、血液学表型及临床表型。方法:选取2022年3月至2023年12月在广西医科大学第一附属医院检查地中海贫血的病例4例。血红蛋白(Hb)分析仪和血细胞分析仪检测全血样本,分析Hb和血常规。Sanger测序法与荧光PCR熔解曲线法检测γ-珠蛋白基因启动子区突变和β-珠蛋白基因突变。结果:共检出^(A)γ-114~-102缺失杂合子4例,Hb分析显示血红蛋白F(Hb F)水平为11.2%~37.8%,血红蛋白A2(Hb A2)水平为2.0%~3.3%,血常规分析显示Hb水平为67~114 g/L,红细胞计数(RBC)为(2.33~4.1)×10^(12)/L,平均红细胞体积(MCV)为84.02~91.9 fL,平均红细胞血红蛋白(MCH)为27.8~29.7 pg。γ-珠蛋白基因及β-珠蛋白基因突变检测结果表明:4例病例含有^(A)γ-114~-102缺失杂合子,其中2例合并有^(G)γ-158C>T突变杂合子;4例病例均合并有β-珠蛋白基因突变,基因型分别为Codon 41-42(-TTCT)杂合子突变、Codon 41-42(-TTCT)纯合子突变、IVS-Ⅱ-654(C>T)复合Codon 41-42(-TTCT)突变和Codon17(A>T)复合Codon 71-72(+A)突变。结论:首次在中国人群中发现^(A)γ-114~-102缺失杂合子,且复合β-地中海贫血的病例,临床表现为轻度或中度贫血。^(A)γ-114~-102缺失突变导致非缺失型遗传性持续性胎儿血红蛋白综合征(nd-HPFH),能够减轻β-地中海贫血患者的贫血程度。Objective:To study the gene mutation types,hematologic phenotypes and clinical phenotype of the deletion mutations in the promoter region-114 to-102 of^(A)γ-globin gene.Methods:Four cases for thalassemia screening in the First Affiliated Hospital of Guangxi Medical University from March 2022 to December 2023 were selected.Hemoglobin(Hb)analyzer and blood cell analyzer were used to test whole blood samples for Hb analysis and blood routine.The mutations ofγ-globin gene promoter region andβ-globin gene were detected by Sanger sequencing and fluorescence PCR melting curve analysis.Results:A total of 4 cases with^(A)γ-114 to-102 deletional heterozygotes were detected.The results of Hb analysis showed that fetal hemoglobin(Hb F)levels were 11.2%-37.8%and 2.0%-3.3%for hemoglobin A2(Hb A2).The results of blood routine analysis showed that Hb level was 67 g/L-114 g/L,red blood cell count(RBC)(2.33-4.1)×10^(12)/L,mean corpuscular volume(MCV)was 84.02 fL-91.9 fL,and mean corpuscular hemoglobin(MCH)was 27.8 pg-29.7 pg.The genotype analysis forγ-globin gene promoter region andβ-globin gene showed that 4 cases were heterozygotes for^(A)γ-114 to-102 deletion,and two of them combined with heterozygotes^(G)γ-158C>T gene mutation.All 4 cases hadβ-globin gene mutations.Their genotypes were as follows:heterozygous mutation of Codon 41-42(-TTCT),homozygous mutation of Codon 41-42(-TTCT),compound mutation of IVS-Ⅱ-654(C>T)and Codon 41-42(-TTCT),and compound mutation of Codon17(A>T)and Codon 71-72(+A).Conclusion:^(A)γ-114 to-102 deletional heterozygote and coinheritedβ-thalassemia are first identified in Chinese population,presenting with mild or moderate clinical manifestations.^(A)γ-114 to-102 deletional mutation causes non-deletional hereditary persistence of fetal hemoglobin(nd-HPFH),and it can reduce the clinical severity in patients withβ-thalassemia.

关 键 词：γ-珠蛋白基因启动子 非缺失型遗传性持续性胎儿血红蛋白综合征 Β-地中海贫血 

分 类 号：R556.7[医药卫生—血液循环系统疾病]