355例产前胎儿羊水细胞易位染色体核型分析及遗传咨询
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摘要
目的分析产前羊水穿刺孕妇胎儿的易位染色体类型、遗传方式和断点,为易位染色体携带者的再发风险及妊娠结局提供遗传咨询和诊断意见。方法彩超辅助抽取羊水,常规方法进行细胞培养、收获、制片、G显带、核型分析,回顾性统计分析2014年1月～2018年9月胎儿染色体易位的发生率、常见核型、遗传方式和断点。结果 13 100例产检孕妇中共检测出355例胎儿染色体易位,发生率为2.71%(355/13 100)。临床特征为植入前产前诊断、女方为携带者和男方为携带者的检出率最多,遗传方式为父系遗传或母系遗。rob(13;14)和rob(14;21)是累及次数最多的罗氏易位核型,t(11;22)和t(4;18)是累及次数最多的相互易位核型,遗传方式以父系遗传或母系遗传。断点分析显示,相互易位染色体共累及出现482个断点,其中断点11q23、22q11和12q24累及次数最多。结论本研究的孕妇胎儿易位染色体发生率较高,rob(13;14)和t(11;22)是累及次数最多的罗氏和相互易位核型,父系遗传或母系遗传。11q23、22q11和12q24是累及次数最多的相互易位断点。分析孕妇胎儿易位染色体发生率、遗传方式、核型和断点可能易位染色体携带者的再发风险及妊娠结局提供遗传咨询和诊断意见。
Objective:Analyze the translocation chromosome type,genetic pattern and breakpoints of the fetus of pregnant women with prenatal amniocentesis,and to provide genetic counseling and diagnostic advice for the recurrence risk and pregnancy outcome of translocated carriers. Methods:Amniotic fluid was extracted by color ultrasound,and cell culture,harvest,preparation,G-band and karyotype analysis were performed by conventional methods. Incidence,common karyotypes,genetic methods and breakpoints of fetal chromosomal translocation were analyzed retrospectively from January 2014 to September 2018.Results:A total of 355 fetal chromosomal translocation were detected in 13,100 pregnant women,with an incidence of 2.71%(355/13,100). The clinical features for preimplantation genetic diagnosis(PGD),female carrier and male carrier were the highest detection rate,which was inherited by paternal or maternal inheritance. Rob(13;14)and rob(14;21)were the most involved robertsonian translocation karyotype,t(11;22)and t(4;18)were the most frequently involved type of reciprocal translocation karyotype. Breakpoint analysis showed that 482 break points were involved in the translocation chromosomes,among which the breakpoints 11 q23,22 q11 and 12 q24 were most involved. Conclusion:The incidence of fetal translocation chromosomes in pregnant women in this study is relatively high,rob(13;14)and t(11;22)is the most involved robertsonian and reciprocal translocation karyotype,and the genetic mode is paternal or maternal. 11 q23,22 q11 and 12 q24 is the most involved breakpoints.Analysis the incidence,genetic pattern,karyotype and breakpoint may be provide genetic counseling and diagnostic advice for the risk of recurrence and pregnancy outcome of the translocated carriers.
Objective:Analyze the translocation chromosome type,genetic pattern and breakpoints of the fetus of pregnant women with prenatal amniocentesis,and to provide genetic counseling and diagnostic advice for the recurrence risk and pregnancy outcome of translocated carriers. Methods:Amniotic fluid was extracted by color ultrasound,and cell culture,harvest,preparation,G-band and karyotype analysis were performed by conventional methods. Incidence,common karyotypes,genetic methods and breakpoints of fetal chromosomal translocation were analyzed retrospectively from January 2014 to September 2018.Results:A total of 355 fetal chromosomal translocation were detected in 13,100 pregnant women,with an incidence of 2.71%(355/13,100). The clinical features for preimplantation genetic diagnosis(PGD),female carrier and male carrier were the highest detection rate,which was inherited by paternal or maternal inheritance. Rob(13;14)and rob(14;21)were the most involved robertsonian translocation karyotype,t(11;22)and t(4;18)were the most frequently involved type of reciprocal translocation karyotype. Breakpoint analysis showed that 482 break points were involved in the translocation chromosomes,among which the breakpoints 11 q23,22 q11 and 12 q24 were most involved. Conclusion:The incidence of fetal translocation chromosomes in pregnant women in this study is relatively high,rob(13;14)and t(11;22)is the most involved robertsonian and reciprocal translocation karyotype,and the genetic mode is paternal or maternal. 11 q23,22 q11 and 12 q24 is the most involved breakpoints.Analysis the incidence,genetic pattern,karyotype and breakpoint may be provide genetic counseling and diagnostic advice for the risk of recurrence and pregnancy outcome of the translocated carriers.
引文
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[13]Kim J W,et al.Complex chromosomal rearrangements in infertile males:complexity of rearrangement affects spermatogenesis[J]Fertil Steril,2011,95(1):349-352,351-352.
[14]Bugge M,Bruun-Petersen G,Brondum-Nielsen K,et al.Disease associated balanced chromosome rearrangements:a resource for large scale genotype-phenotype delineation in man[J].J Med Genet,2000,37(11):858-865.
[2]Kaihui Z,Yan H,Rui D,et al.Familial intellectual disability as a result of a derivative chromosome 22 originating from a balanced translocation(3;22)in a four generation family[J].Mol Cytogenet,2018,11:18.
[3]Alhalabi N,Al-Achkar W,Wafa A,et al.De novo Balanced Robertsonian Translocation rob(22;22)(q10;q10)in a Woman with Recurrent Pregnancy Loss:A Rare Case[J].J Reprod Infertil,2018,19(1):61-66.
[4]Hu L,Cheng D,Gong F,et al.Reciprocal Translocation Carrier Diagnosis in Preimplantation Human Embryos[J].EBioMedicine,2016,14:139-147.
[5]Xu J,Zhang Z,Niu W,et al.Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos[J].Proc Natl Acad Sci U S A,2017,114(41):E8695-E8702.
[6]张雯珂.Mate pair文库测序在染色体相互易位PGD中的应用[D].中国人民解放军医学院,2016.
[7]Zhang S,Lei C,Wu J,et al.The establishment and application of preimplantation genetic haplotyping in embryo diagnosis for reciprocal and Robertsonian translocation carriers[J].BMC Med Genomics,2017,10(1):60.
[8]Geraedts J,Montag M,Magli M C,et al.Polar body array CGHfor prediction of the status of the corresponding oocyte.Part I:clinical results[J].Hum Reprod,2011,26(11):3173-3180.
[9]傅文婷,等.11例t(11;22)(q23;q11)染色体平衡易位患者的临床与遗传学分析[J].重庆医学,2018(20):2700-2702.
[10]Kurahashi H,et al.The constitutional t(11;22):implications for a novel mechanism responsible for gross chromosomal rearrangements[J].Clin Genet,2010,78(4):299-309.
[11]肖冰,季星,张静敏,等.额外der(22)t(11;22)综合征1例报告[J].临床儿科杂志,2011(09):889-890.
[12]Morin S J,et al.Translocations,inversions and other chromosome rearrangements[J].Fertil Steril,2017,107(1):19-26.
[13]Kim J W,et al.Complex chromosomal rearrangements in infertile males:complexity of rearrangement affects spermatogenesis[J]Fertil Steril,2011,95(1):349-352,351-352.
[14]Bugge M,Bruun-Petersen G,Brondum-Nielsen K,et al.Disease associated balanced chromosome rearrangements:a resource for large scale genotype-phenotype delineation in man[J].J Med Genet,2000,37(11):858-865.