云南4种罕见异常血红蛋白突变型分析
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摘要
目的明确7例血红蛋白电泳检出的异常条带产生的基因分子基础,探讨基因型与血液学表型的关系。方法用血常规指标和血红蛋白电泳进行表型分析,采用PCR-反向点杂交法检测α地贫和β地贫,应用PCR产物测序技术对α、β基因全长进行测序,检测基因突变类型。结果 7例样本中检出4种异常血红蛋白突变型:1例中国首次发现的Hb San Bruno(HBB:c.120G>C)、2例Hb New York(HBB:c.341T>A)、2例Hb J-Bangkok(HBB:c.170G>A)、2例Hb G-Coushatta(HBB:c.68A>C),血常规参数均无明显异常。结论云南存在多种异常血红蛋白突变型,多数单纯异常血红蛋白罕见突变都不产生临床表型,但是云南作为地中海贫血的高发地区,异常血红蛋白病合并地中海贫血的临床意义和危害性有待于进一步研究。
Objective To determine the molecular basis of the 7 abnormal hemoglobin(Hb)cases,and to explore the relationship between genotype and hematological phenotype.Methods Complete blood counts and quantification of Hb levels performed by capillary electrophoresis were used to hematological analysis.The PCR-reverse dot blot was used to detectαandβthalassemia and the molecular characterization was performed using sanger squencing.Results 4 different Hb variants were detected:one case of Hb San Bruno(HBB:c.120 G>C),2 cases of Hb New York(HBB:c.341 T >A),2 cases of Hb j-bangkok(HBB:c.170 G>A),and 2 cases of Hb G-Coushatta(HBB:c.68 A>C).All the cases are hematological normalities.Conclusion Most of the rare Hb mutations clinical are asymptomatic,but the impact of its combination with thalassemia remains to be further studied.
Objective To determine the molecular basis of the 7 abnormal hemoglobin(Hb)cases,and to explore the relationship between genotype and hematological phenotype.Methods Complete blood counts and quantification of Hb levels performed by capillary electrophoresis were used to hematological analysis.The PCR-reverse dot blot was used to detectαandβthalassemia and the molecular characterization was performed using sanger squencing.Results 4 different Hb variants were detected:one case of Hb San Bruno(HBB:c.120 G>C),2 cases of Hb New York(HBB:c.341 T >A),2 cases of Hb j-bangkok(HBB:c.170 G>A),and 2 cases of Hb G-Coushatta(HBB:c.68 A>C).All the cases are hematological normalities.Conclusion Most of the rare Hb mutations clinical are asymptomatic,but the impact of its combination with thalassemia remains to be further studied.
引文
[1]XIONG F,SUN M,ZHANG X,et al.Molecular epidemiological survey of haemoglobinopathies in the Guangxi Zhuang Autonomous Region of southern China[J].Clin Genet,2010,78(2):139-148.
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[8]赵颖,商璇,熊符,等.异常血红蛋白(Hb J-Bangkok)合并β-地中海贫血的临床表型分析[J].中华医学遗传学杂志,2013,30(2):148-151.
[9]张强,范歆,何升,等.Hb New York病ARMS-PCR检测及临床表型分析[J].临床检验杂志,2014,32(9):706-707.
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[11]赖兆新,严伟玲.血红蛋白G病检验结果分析[J].国际检验医学杂志,2015,36(18):2755-2757.
[12]王妍,林敏,韩志君,等.江苏省无锡地区异常血红蛋白病的流行病学调查[J].实用医学杂志,2012,28(2):316-318.
[13]莫桂玲,胡朝晖,张玲,等.我国罕见异常血红蛋白突变型[β43(CD2)Glu→Lys]分析[J].国际检验医学杂志,2010,31(9):918-919.
[14]葛世军.不稳定血红蛋白Hb Rush的血液学表型和基因型分析[J].中华医学遗传学杂志,2017,34(1):15-20.
[15]LAI K,HUANG G,SU L,et al.The prevalence of thalassemia in mainland China:evidence from epidemiological surveys[J].Sci Rep,2017,7(1):920.
[16]DE LA FUENTE-GONZALO F,NIETO J M,VELAS-CO D,et al.HB Puerta del Sol[HBA1:c.148A>C],HBValdecilla[HBA2:c.3G>T],HB Gran Via[HBA2:c.98T>G],HB Macarena[HBA2:c.358C>T]and HB El Retiro[HBA2:c.364_366dupGTG]:description of five new hemoglobinopathies[J].Clin Chem Lab Med,2016,54(4):553-560.
[17]XU A,CHEN W,XIA Y,et al.Effects of common hemoglobin variants on HbA1cmeasurements in China:results for alpha-and beta-globin variants measured by six methods[J].Clin Chem Lab Med,2018,56(8):1353-1361.
[18]ZHANG X M,WEN D M,XU S N,et al.Effects of hemoglobin variants HbJ Bangkok,HbE,HbG Taipei,and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography[J].J Clin Lab Anal,2018,32(1):e22214
[19]索明环,温冬梅,王伟佳,等.5个糖化血红蛋白检测系统对Hb NewYork合并β地中海贫血标本异常结果预警能力比较[J].临床检验杂志,2017,35(9):649-653.
[2]PATRINOS G P,GIARDINE B,RIEMER C,et al.Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies[J].Nucleic Acids Res,2004,32(Database issue):D537-D541.
[3]ZENG Y T,HUANG S Z.Disorders of haemoglobin in China[J].J Med Gene,1987,24(10):578-583.
[4]秦良谊.我国异常血红蛋白发生率、分布及遗传多态性[J].医学研究通讯,2003,32(12):12-14.
[5]HE J,ZENG X,ZHANG Y,et al.Prevalence of hemoglobin E in Yunnan Province of Southwest China[J].Hematology,2016,21(1):54-59.
[6]莫宗平,张玲,喻长顺,等.异常血红蛋白81例基因分析[J].广东医学,2012,33(3):338-341.
[7]HOYER J D,MCCORMICK D J,SNOW K,et al.Four new beta chain hemoglobin variants without clinical or hematological effects:Hb San Bruno[beta39(C5)Gln-->His];Hb Fort Dodge[beta93(F9)Cys-Tyr];Hb Rhode Island[beta116(G18)His-->Tyr];and Hb Inglewood[beta142(H20)Ala-->Thr][J].Hemoglobin,2002,26(3):299-303.
[8]赵颖,商璇,熊符,等.异常血红蛋白(Hb J-Bangkok)合并β-地中海贫血的临床表型分析[J].中华医学遗传学杂志,2013,30(2):148-151.
[9]张强,范歆,何升,等.Hb New York病ARMS-PCR检测及临床表型分析[J].临床检验杂志,2014,32(9):706-707.
[10]ZHANG J,HE J,MAO X,et al.Haematological and electrophoretic characterisation ofβ-thalassaemia in Yunnan province of Southwestern China[J].BMJ Open,2017,7(1):e013367.
[11]赖兆新,严伟玲.血红蛋白G病检验结果分析[J].国际检验医学杂志,2015,36(18):2755-2757.
[12]王妍,林敏,韩志君,等.江苏省无锡地区异常血红蛋白病的流行病学调查[J].实用医学杂志,2012,28(2):316-318.
[13]莫桂玲,胡朝晖,张玲,等.我国罕见异常血红蛋白突变型[β43(CD2)Glu→Lys]分析[J].国际检验医学杂志,2010,31(9):918-919.
[14]葛世军.不稳定血红蛋白Hb Rush的血液学表型和基因型分析[J].中华医学遗传学杂志,2017,34(1):15-20.
[15]LAI K,HUANG G,SU L,et al.The prevalence of thalassemia in mainland China:evidence from epidemiological surveys[J].Sci Rep,2017,7(1):920.
[16]DE LA FUENTE-GONZALO F,NIETO J M,VELAS-CO D,et al.HB Puerta del Sol[HBA1:c.148A>C],HBValdecilla[HBA2:c.3G>T],HB Gran Via[HBA2:c.98T>G],HB Macarena[HBA2:c.358C>T]and HB El Retiro[HBA2:c.364_366dupGTG]:description of five new hemoglobinopathies[J].Clin Chem Lab Med,2016,54(4):553-560.
[17]XU A,CHEN W,XIA Y,et al.Effects of common hemoglobin variants on HbA1cmeasurements in China:results for alpha-and beta-globin variants measured by six methods[J].Clin Chem Lab Med,2018,56(8):1353-1361.
[18]ZHANG X M,WEN D M,XU S N,et al.Effects of hemoglobin variants HbJ Bangkok,HbE,HbG Taipei,and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography[J].J Clin Lab Anal,2018,32(1):e22214
[19]索明环,温冬梅,王伟佳,等.5个糖化血红蛋白检测系统对Hb NewYork合并β地中海贫血标本异常结果预警能力比较[J].临床检验杂志,2017,35(9):649-653.