中国武汉地区新生儿β-地中海贫血基因型分析
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摘要
目的:调查中国武汉地区新生儿β-地中海贫血基因型,以及分子流行病学特征。方法:采用PCR-流式荧光杂交法检测2721例地中海贫血初筛阳性的新生儿β-地中海贫血基因。结果:在中国武汉地区检测出新生儿β-地中海贫血537例,α-复合β-地中海贫血19例。β-地中海贫血以轻型为主;中间型1例,其基因型为-29/IVS-2-654;重型2例,其基因型分别为CD41-42/IVS-2-654和CD27-28/IVS-2-654。在537例β-地中海贫血患儿中检测出15种基因型,以点突变IVS-2-654/N 229例(42.64%)、CD41-42/N 121例(22.53%)、CD17/N 76例(14.15%)、CD26/N 39例(7.26%)和CD27-28/N 27例(5.03%)为主,占β-地中海贫血的90%以上。β-地中海贫血基因频率IVS-2-654突变、CD41-42突变和CD17突变出现的频率高,其构成比分别为:42.93%、22.36%和14.13%。结论:中国武汉地区新生儿β-地中海贫血以轻型为主,其基因频率以IVS-2-654突变、CD41-42突变和CD17突变较高。
Objective: To investigate the β-thalassemia genotypes in neonates in Wuhan area of China and their characteristics of molecular epidemiology. Methods: A total of 2721 neonates in Wuhan who were positive in primary screening for β-thalassemia were included in this study. Genotypes of β-thalassemia gene were determined with PCRflow cytometry and fluorescence hybridization assay. Results: There were 537 cases of β-thalassemia with over 15 kinds of genotypes, and 19 cases of α-composite β-thalassemia with 8 genotypes. Thalassemia minor appeared mostly in β-thalassemia, including 229 cases of IVS-2-654/N(42.64%), 121 cases of CD41-42/N(22.53%), 76 cases of CD17/N(14.15%), 39 cases of CD26/N(7.26%) and 27 cases of CD27-28/N(5.03%) and the total ratio reached to 91.62%, however, 1 case of thalassemia intermediate was-29/IVS-2-654, and the genotype of 2 cases of thalassemia major was CD27-28/IVS-2-654 and CD41-42/IVS-2-654. The mutation frequency of IVS-2-654, CD41-42 and CD17 was higher in β-thalassemia, as follows: 42.93%, 22.36% and 14.13%, respectively. Conclusion: β-Thalassemia minor is the majority of the neonants thalassemia in Wuhan area. The gene frequency of deletion type, such as IVS-2-654/N, CD41-42/N and CD17/N, is higher.
Objective: To investigate the β-thalassemia genotypes in neonates in Wuhan area of China and their characteristics of molecular epidemiology. Methods: A total of 2721 neonates in Wuhan who were positive in primary screening for β-thalassemia were included in this study. Genotypes of β-thalassemia gene were determined with PCRflow cytometry and fluorescence hybridization assay. Results: There were 537 cases of β-thalassemia with over 15 kinds of genotypes, and 19 cases of α-composite β-thalassemia with 8 genotypes. Thalassemia minor appeared mostly in β-thalassemia, including 229 cases of IVS-2-654/N(42.64%), 121 cases of CD41-42/N(22.53%), 76 cases of CD17/N(14.15%), 39 cases of CD26/N(7.26%) and 27 cases of CD27-28/N(5.03%) and the total ratio reached to 91.62%, however, 1 case of thalassemia intermediate was-29/IVS-2-654, and the genotype of 2 cases of thalassemia major was CD27-28/IVS-2-654 and CD41-42/IVS-2-654. The mutation frequency of IVS-2-654, CD41-42 and CD17 was higher in β-thalassemia, as follows: 42.93%, 22.36% and 14.13%, respectively. Conclusion: β-Thalassemia minor is the majority of the neonants thalassemia in Wuhan area. The gene frequency of deletion type, such as IVS-2-654/N, CD41-42/N and CD17/N, is higher.
引文
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14戴庆福,李晓璐,王玉霞,等.中国福建省龙岩地区地中海贫血基因突变类型的分析.中国实验血液学杂志,2017;25(2):498-502.
15黄利华,刘冬霞,李伟明,等.广东清远地区β-地中海贫血基因型特点.暨南大学学报(自然科学与医学版),2017;38(1):41-45.
16 Yao XY,Yu J,Chen SP,et al.Prevalence and genetic analysis of alpha-thalassemia and beta-thalassemia in Chongqing area of China.Gene,2013;532(1):120-124.
17 Yao H,Chen X,Lin L,et al.The spectrum of alpha-and betathalassemia mutations of the Li people in Hainan Province of China.Blood Cells Mol Dis,2014;53(1-2):16-20.
18蔡文倩,胡晞江,熊乾,等.中国武汉地区新生儿α-地中海贫血基因型分析.中国实验血液学杂志,2018,26(1):219-222.
19肖晗,向赟,孙红,等.武汉地区儿童β地中海贫血基因突变类型分析.生物医学工程与临床,2015,(5):515-518.
20童芳芳,孙慧,方小桂.武汉地中海贫血流行病学调查及基因突变类型与频率分析.中华实用诊断与治疗杂志,2015,(8):759-760.
21 Byrou S,Makrigiorgos GM,Christofides A,et al.Fast TemperatureGradient COLD PCR for the enrichment of the paternally inherited SNPs in cell free fetal DNA;an application to non-invasive prenatal diagnosis of beta-thalassaemia.PLoS One,2018;13(7):e0200348.
2 Lai K,Huang G,Su L,et al.The prevalence of thalassemia in mainland China:evidence from epidemiological surveys.Sci Rep,2017;7(1):920.
3 Xiong F,Sun M,Zhang X,et al.Molecular epidemiological survey of haemoglobinopathies in the Guangxi Zhuang Autonomous Region of southern China.Clin Genet,2010;78(2):139-148.
4 Wang H,Naghavi M,Allen C,et al.Global,regional,and national life expectancy,all-cause mortality,and cause-specific mortality for 249 causes of death,1980-2015:a systematic analysis for the Global Burden of Disease Study 2015.Lancet,2016;388(10053):1459-1544.
5 He S,Wang L,Pan P,et al.Etiology and perinatal outcome of nonimmune hydrops fetalis in Southern China.AJP Rep,2017;7(2):e111-e115.
6 Jaripour ME,Hayatigolkhatmi K,Iranmanesh V,et al.Prevalence of beta-thalassemia mutations among northeastern Iranian population and their Impacts on hematological indices and application of prenatal diagnosis,a seven-years study.Mediterr J Hematol Infect Dis,2018;10(1):e2018042.
7 Zhang J,He J,Mao X,et al.Haematological and electrophoretic characterisation of beta-thalassaemia in Yunnan province of South western China.BMJ Open,2017;7(1):e013367.
8付月,刘文君.地中海贫血实验室诊断研究进展.中国实验血液学杂志,2018;26(2):631-636.
9 Suwannakhon N,Pongsawatkul K,Seeratanachot T,et al.The shortcut strategy for beta thalassemia prevention.Hematol Rep,2018;10(2):7530.
10李华,何旭霞.广州市黄埔区5306对夫妇孕期地中海贫血的筛查与诊断分析.中国妇产科临床杂志,2016;17(01):37-39.
11 Giordano PC.Newborn screening for hemoglobinopathies using capillary electrophoresis.Clinical Applications of Capillary Electrophoresis.Humana Press,2013:131-145.
12杨阳,张杰.中国南方地区地中海贫血研究进展.中国实验血液学杂志,2017,25(1):276-280.
13 Zhao P,Weng R,Wu H.Molecular spectrum of alpha-and betathalassemia mutations in a large Ethnic Hakka Population in Southern China.Hemoglobin,2018;42(2):117-121.
14戴庆福,李晓璐,王玉霞,等.中国福建省龙岩地区地中海贫血基因突变类型的分析.中国实验血液学杂志,2017;25(2):498-502.
15黄利华,刘冬霞,李伟明,等.广东清远地区β-地中海贫血基因型特点.暨南大学学报(自然科学与医学版),2017;38(1):41-45.
16 Yao XY,Yu J,Chen SP,et al.Prevalence and genetic analysis of alpha-thalassemia and beta-thalassemia in Chongqing area of China.Gene,2013;532(1):120-124.
17 Yao H,Chen X,Lin L,et al.The spectrum of alpha-and betathalassemia mutations of the Li people in Hainan Province of China.Blood Cells Mol Dis,2014;53(1-2):16-20.
18蔡文倩,胡晞江,熊乾,等.中国武汉地区新生儿α-地中海贫血基因型分析.中国实验血液学杂志,2018,26(1):219-222.
19肖晗,向赟,孙红,等.武汉地区儿童β地中海贫血基因突变类型分析.生物医学工程与临床,2015,(5):515-518.
20童芳芳,孙慧,方小桂.武汉地中海贫血流行病学调查及基因突变类型与频率分析.中华实用诊断与治疗杂志,2015,(8):759-760.
21 Byrou S,Makrigiorgos GM,Christofides A,et al.Fast TemperatureGradient COLD PCR for the enrichment of the paternally inherited SNPs in cell free fetal DNA;an application to non-invasive prenatal diagnosis of beta-thalassaemia.PLoS One,2018;13(7):e0200348.