α2珠蛋白基因突变IVS-Ⅱ-55(T→G)的临床表型分析
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摘要
目的鉴定一种α2-珠蛋白基因突变类型,分析携带者的表型特征。方法收集5个携带α2-珠蛋白基因IVS-Ⅱ-55(T→G)杂合突变的婴幼儿先证者的家系和3例散发成人携带者的外周血样本进行血常规和血红蛋白电泳分析,并采用跨越断裂点聚合酶链反应(Gap-PCR)方法、PCR结合反向点杂交(PCR-RDB)法以及DNA测序方法进行珠蛋白基因缺失和突变的鉴定。结果 13例α2-珠蛋白基因IVS-Ⅱ-55(T→G)杂合突变携带者中,5例婴幼儿先证者的MCV和MCH均低于正常参考区间,表现为小细胞低色素轻中度贫血;成人(包括3例散发成人和5例家系中的成人携带者)中1例表现为小细胞低色素中度贫血,1例复合βCD27-28杂合突变表现为MCV 65 fL、MCH 20.3 pg,1例复合SEA-HPFH表现为MCV 81.9 fL、MCH 26.5 pg,其余MCV和MCH均正常; IVS-Ⅱ-55复合βCD27-28杂合突变的HbA_2为5.8%。IVS-Ⅱ-55复合SEA-HPFH的HbA_2为3.0%,Hb F为29.0%。单纯IVS-Ⅱ-55杂合子的HbA_2均正常。所有携带者均未见异常血红蛋白条带。结论单纯IVS-Ⅱ-55(T→G)杂合子的血液学表型正常,复合β地贫时表型与单纯β地贫类似。
Objective To identify a α-globin gene mutation-IVS-Ⅱ-55(T→A) and analyze hematological characteristics of IVS-Ⅱ-55(T→G) carriers.Methods The peripheral blood samples were collected from the members of five family and three sporadic IVS-Ⅱ-55(T→G) carriers for the analysis of RBC parameters and hemoglobin electrophoresis.Gap-PCR,PCR-RDB(reverse dot blot)and DNA sequencing were carried out for the identification of gene deletion and mutation of α-globin and β-globin.Results The results of RBC parameters of five infant probands which presented with microcytic hypochromic anemia were below the normal reference interval.One of the adult carriers of IVS-Ⅱ-55(T→G) heterozygote alone presented with microcytic hypochromic anemia,and the others showed normal RBC parameters.The hematological phenotype index(MCV,MCH and HbA_2) of one adult carrying a compound heterozygote for IVS-Ⅱ-55(T→G) and βCD27-28 M/Nwere 65.0 fL,20.3 pg and 5.8% respectively.The hematological phenotype index(MCV,MCH,HbA_2 and Hb F) of one adult carrying a compound heterozygote for IVS-Ⅱ-55(T→G) and SEA-HPFH were 81.9 fL,26.5 pg,3.0% and 29.0% respectively.The HbA_2 levels of all carriers of IVS-Ⅱ-55(T→G) heterozygote alone were in normal range.No abnormal hemoglobin band was detectable on hemoglobin electrophoresis for all the carries.Conclusion The carriers of IVS-Ⅱ-55(T→G) heterozygote alone were asymptomatic.The phenotype of compound heterozygote for β-thalassemia was similar to that of β-thalassemia alone.
Objective To identify a α-globin gene mutation-IVS-Ⅱ-55(T→A) and analyze hematological characteristics of IVS-Ⅱ-55(T→G) carriers.Methods The peripheral blood samples were collected from the members of five family and three sporadic IVS-Ⅱ-55(T→G) carriers for the analysis of RBC parameters and hemoglobin electrophoresis.Gap-PCR,PCR-RDB(reverse dot blot)and DNA sequencing were carried out for the identification of gene deletion and mutation of α-globin and β-globin.Results The results of RBC parameters of five infant probands which presented with microcytic hypochromic anemia were below the normal reference interval.One of the adult carriers of IVS-Ⅱ-55(T→G) heterozygote alone presented with microcytic hypochromic anemia,and the others showed normal RBC parameters.The hematological phenotype index(MCV,MCH and HbA_2) of one adult carrying a compound heterozygote for IVS-Ⅱ-55(T→G) and βCD27-28 M/Nwere 65.0 fL,20.3 pg and 5.8% respectively.The hematological phenotype index(MCV,MCH,HbA_2 and Hb F) of one adult carrying a compound heterozygote for IVS-Ⅱ-55(T→G) and SEA-HPFH were 81.9 fL,26.5 pg,3.0% and 29.0% respectively.The HbA_2 levels of all carriers of IVS-Ⅱ-55(T→G) heterozygote alone were in normal range.No abnormal hemoglobin band was detectable on hemoglobin electrophoresis for all the carries.Conclusion The carriers of IVS-Ⅱ-55(T→G) heterozygote alone were asymptomatic.The phenotype of compound heterozygote for β-thalassemia was similar to that of β-thalassemia alone.
引文
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[10]宋春林,刘正平,陈淑芬.二代高通量测序仪在大规模地中海贫血基因检测的应用价值[J].中国医疗设备,2016,31(Suppl):15.
[2]Harteveld CL,Heister JG,Giordano PC,et al.An IVS 1-116(A->G)acceptor splice site mutation in the alpha 2 globin gene causing alpha+thalassaemia in two Dutch families[J].Br J Haematol,1996,95(3):461-466.
[3]Harteveld CL,Jebbink MC,vander Lely N,et al.Alpha-thalassemia phenotype induced by the new IVS-Ⅱ-2(T->A)splice donor site mutation on the alpha2-globin genes[J].Hemoglobin,2006,30(1):3-7.
[4]Orkin SH,Goff SC,Hechtman RL,et al.Mutation in an intervening sequence splice junction in man[J].Proc Natl Acad Sci USA,1981,78(8):5041-5045.
[5]Felber BK,Orkin SH,Hamer DH.Abnormal RNA splicing causes one form of alpha thalassemia[J].Cell,1982,29(3):895-902.
[6]Pagani F,Buratti E,Stuani,et al.A new type of mutation causes a splicing defect in ATM[J].Nat Genet,2002,30(4):426-429.
[7]荣卡彬,黄革,蒋文玲,等.中间型β地中海贫血家系基因分子生物学特征分析[J].中华检验医学杂志,2009,32(4):412-416.
[8]陈文璟,温旺荣,苏运钦,等.用巢氏PCR检测防止香港型地中海贫血漏诊[J].临床检验杂志,2014,32(8):713-715.
[9]谢武琼.地中海贫血基因检测及干预研究进展[J].中国优生与遗传杂志,2016,24(8):4-6.
[10]宋春林,刘正平,陈淑芬.二代高通量测序仪在大规模地中海贫血基因检测的应用价值[J].中国医疗设备,2016,31(Suppl):15.