罕见β-珠蛋白基因突变导致儿童β-地中海贫血的研究  

Study on rareβ-globin gene mutations causingβ-thalassemia in children

作　　者：吕璐玙 林伟雄[2,3,4] 肖璇 陈萍[1,2,3,4] 张学 Lyu Luyu;Lin Weixiong;Xiao Xuan;Chen Ping;Zhang Xue(Department of Pediatrics,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Guangxi Key Laboratory of Thalassemia Research,Guangxi Medical University,Nanning 530021,China;Key Laboratory of Thalassemia Medicine,Chinese Academy of Medical Sciences,Nanning 530021,China;NHC Key Laboratory of Thalassemia Medicine,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院儿科,南宁530021 [2]广西医科大学广西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重点实验室,南宁530021 [4]国家卫生健康委员会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》2023年第6期906-910,共5页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81960574);广西重点实验室建设项目(No.22-035-24)。

摘　　要：目的:研究儿童罕见β-地中海贫血(β-地贫)的β-珠蛋白基因突变类型、血液学特征和临床表现。方法:选取广西医科大学第一附属医院2022年1—12月检测地中海贫血的病例。血细胞分析仪行血常规检测,高效液相色谱法行血红蛋白(Hb)分析;跨越断裂点聚合酶链反应(Gap-PCR)法、荧光PCR熔解曲线法和DNA测序检测α-地中海贫血(α-地贫)和β-地贫基因突变。结果:共检出99例β-地贫患儿,其中2例为罕见β-珠蛋白基因突变导致β-地贫的患儿。病例1为1岁女患儿,轻度贫血,血常规示Hb 101.00 g/L,红细胞计数(RBC)5.43×10^(12)/L,红细胞平均体积(MCV)56.90 fL,红细胞平均血红蛋白量(MCH)18.60 pg,红细胞平均血红蛋白浓度(MCHC)327.00 g/L,红细胞比容(HCT)0.31 L/L和红细胞体积分布宽度(RDW)0.19;Hb分析结果示Hb A25.70%,Hb F 2.60%。基因分析及DNA测序结果显示β-珠蛋白基因IVS-Ⅰ-2(T>C)突变杂合子。病例2为6岁男孩,轻度贫血,血常规示Hb 94.90 g/L,RBC 4.97×10^(12)/L,MCV 59.97 fL,MCH 19.11 pg,MCHC 318.70 g/L,HCT 0.30 L/L,RDW 0.15;Hb分析结果示Hb A25.80%,Hb F 1.90%。基因分析及DNA测序结果显示β-珠蛋白基因CD95(+A)杂合子突变。结论:首次在国内发现β-珠蛋白基因CD95(+A)杂合子突变导致β-地贫的患儿,临床表现为轻度贫血,Hb A2水平增高;首次报道国内儿童β-珠蛋白基因IVS-Ⅰ-2(T>C)杂合子β-地贫的血液学特征、Hb分析和临床表现。这两种β-地贫基因突变类型在国内较罕见,提示临床上容易漏诊。Objective:To study the mutation types,hematological characteristics and clinical features of the rareβ-globin gene mutations causingβ-thalassemia(β-thal)in children.Methods:Cases tested for thalassemia were selected in the First Affiliated Hospital of Guangxi Medical University from January 2022 to September 2022.Blood routine tests were performed by a blood cell analyzer.Hemoglobin(Hb)analysis was performed by high performance liquid chromatography.Gap polymerase chain reaction(Gap-PCR),fluorescent PCR melting curve and DNA sequencing were used to detectα-thalassemia(α-thal)andβ-thal gene mutations.Results:A total of 99 cases ofβ-thal in children were detected.Among them,two cases were caused by rareβ-globin gene mutations leading toβ-thal.Case one was a 1-year-old girl with mild anemia,and her blood routine results showed Hb level 101.00 g/L,red blood cell count(RBC)5.43×10^(12)/L,mean corpuscular volume(MCV)56.90 fL,mean corpuscular hemoglobin(MCH)18.60 pg,mean corpuscular hemoglobin concentration(MCHC)327.00 g/L,hematocrit(HCT)level 0.31 L/L and red blood cell distribution width(RDW)0.19;Hb analysis showed that Hb A2 and Hb F were 5.70%and 2.60%,respectively.Gene analysis and DNA sequencing results showed that it was aβ-globin gene IVS-Ⅰ-2(T>C)mutant heterozygote.Case two was a 6-year-old boy with mild anemia,and his blood routine results showed Hb level 94.90 g/L,RBC 4.97×10^(12)/L,MCV 59.97 fL,MCH 19.11 pg,MCHC 318.70 g/L,HCT level 0.30 L/L and RDW 0.15;Hb analysis showed that Hb A2 was 5.80%and Hb F was 1.90%.Gene analysis and DNA sequencing results showed that it was aβ-globin gene CD95(+A)heterozygous mutation.Conclusion:A heterozygous mutation ofβ-globin gene CD95(+A)is found to causeβ-thal in pediatric patients for the first time in China,which is characterized by mild anemia and increased Hb A2.The hematological characteristics,Hb analysis and clinical phenotype ofβ-thal caused by theβ-globin gene IVS-Ⅰ-2(T>C)mutant heterozygote are reported in the Chinese pediatric cases for the

关 键 词：Β-地中海贫血 罕见突变 临床表现 儿童 

分 类 号：R556[医药卫生—血液循环系统疾病]