分析染色体异常在胎儿复发性流产中的意义
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摘要
目的探讨染色体异常对胎儿复发性流产的意义以及指导染色体异常的夫妇进行妊娠选择。方法使用QFPCR、全基因组高通量测序对流产组织的染色体进行分析,并通过常规G显带技术对夫妇双方进行染色体核型分析。结果通过QF-PCR及全基因组高通量测序(NGS)显示118例复发性流产胎儿中X、16、22号染色体异常所占例数较多,且胎儿染色体异常所占比例为55.9%,说明染色体异常是造成复发性流产的主要因素;通过外周血染色体G显带对15对夫妇进行染色体核型分析,发现有5例染色体异常,核型分别为:1例t(17;19)、3例inv(9)、1例小Y;另外我们发现由父母染色体异常而导致胎儿流产所占比例为16.7%,说明遗传因素是造成胎儿复发性流产的重要因素之一。此外,孕妇年龄及流产次数均与胎儿发生染色体异常而造成的复发性流产密切相关(P<0.05)。结论查找导致胎儿染色体异常的原因对指导流产夫妇再次妊娠有重要意义。
QF-PCR and Genome-wide high-throughput sequencing(NGS)were used to perform chromosome analysis of abortion tissue,and karyotyping was used for chromosomal examination of couples to explore the significance of chromosomal abnormalities on fetal recurrent miscarriage and direct the selection of pregnant couples with chromosomal abnormalities. Amonge118 cases,QF-PCR and genome-wide high-throughput sequencing(NGS)showed that X,16 and 22 had more chromosome abnormalities in fetus with recurrent miscarriage,and the proportion of fetal chromosomal abnormalities was 55.9%,revealing that chromosomal abnormalities is the main cause of recurrent miscarriage. 5 cases of chromosomal abnormalities detected in 15 couples by G-banding analysis,and the karyotypes include 1 t(17;19),3 inv(9)and 1 bit Y. In addition,we found that the proportion of fetal abortion caused by the chromosome abnormality of parents was 16.7%,showing that the genetics is one of the important factors determining the occurrence of fetal recurrent miscarriage. Furthermore,the age of pregnant women and abortion frequency are associated with recurrent miscarriage caused by fetal chromosomal abnormalities(P<0.05). It is great significance to search the reason of recurrent miscarriage caused by chromosomal abnormalities and to guide pregnancy again of abortion couples.
QF-PCR and Genome-wide high-throughput sequencing(NGS)were used to perform chromosome analysis of abortion tissue,and karyotyping was used for chromosomal examination of couples to explore the significance of chromosomal abnormalities on fetal recurrent miscarriage and direct the selection of pregnant couples with chromosomal abnormalities. Amonge118 cases,QF-PCR and genome-wide high-throughput sequencing(NGS)showed that X,16 and 22 had more chromosome abnormalities in fetus with recurrent miscarriage,and the proportion of fetal chromosomal abnormalities was 55.9%,revealing that chromosomal abnormalities is the main cause of recurrent miscarriage. 5 cases of chromosomal abnormalities detected in 15 couples by G-banding analysis,and the karyotypes include 1 t(17;19),3 inv(9)and 1 bit Y. In addition,we found that the proportion of fetal abortion caused by the chromosome abnormality of parents was 16.7%,showing that the genetics is one of the important factors determining the occurrence of fetal recurrent miscarriage. Furthermore,the age of pregnant women and abortion frequency are associated with recurrent miscarriage caused by fetal chromosomal abnormalities(P<0.05). It is great significance to search the reason of recurrent miscarriage caused by chromosomal abnormalities and to guide pregnancy again of abortion couples.
引文
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[3]Rai R,Regan L.Recurrent miscarriage[J].Lancet,2006,368:601-611.
[4]KJ Hyde,DJ Schust,Genetic Considerations in Recurrent Pregnancy Loss[J].Cold Spring Harb Perspect Med,2015,5:a023119.
[5]Chen SP,Tze Kin Lau,Zhang CL,et al.A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing[J].Prenatal Diagnosis,2013,33:584-590.
[6]Zheng H,Jin H,Liu L,et al.Application of next-generation sequencing for 24-chromosome aneuploidy screening of human preimplantation embryos[J].Molecular Cytogenetics,2015,8(1):38.
[7]Frank SO,Jimmy CL,Kingshuk D,et al.Translational utility of next-generation sequencing[J].Genomics,2013,102(3):137-9.
[8]石鑫玮,刘海意,乔福元,等.荧光原位杂交及染色体核型分析在产前诊断中的应用价值[J].中国实用妇科与产科杂志,2011,27(2):125-127.
[9]Papoulidis I,Siomou E,Sotiriadis A,et al.Dual testing with QF-PCR and karyotype analysis for prenatal diagnosis of chromosomal abnormalities.Evaluation of 13500 cases with consideration of using QF-PCR asastand-alone test according to referral indications[J].Prenat Diagn,2012,32(7):680-685.
[10]罗彩群,谢建生,吴维青,等.多重连接依赖探针扩增技术在染色体非整倍体快速产前诊断中的应用[J].中华检验医学杂志,2012,35(2):160-164.
[11]姜利君,陈亚琼,刘国忠.复发性流产的病因学研究进展[J].临床合理用药杂志,2016,9(9):167-169.
[12]Jutta UR,Rajitha P,Pidugu VK,et al.Cytogenetic abnormalities in 1162 couples with recurrent miscarriages in southern region of India:report and review[J].Journal of Assisted Reproduction&Genetics,2011,28:145-149.
[13]袁思敏,廖灿,李东至,等.绒毛细胞培养法分析1983例自然流产胚胎的染色体核型[J].中华妇产科杂志,2017,52(7):461-466.
[14]Xu JW,Zhang Z,Niu WB,et al.Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos[J].PNAS,2017,114(41):E8695-E8702.
[15]Sepulveda W,Cullen S,Nicolaidis P,et al.Echogenic foci in the fetal heart:a marker of chromosomal abnormality[J].BJOG,1995,102:490-492.
[16]夏家辉.医学遗产学讲座[M].湖南科学技术出版社,1998,22.