新发染色体异常对罗氏易位和相互易位携带者植入前遗传学诊断的影响分析
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摘要
目的探讨植入前遗传学诊断(PGD)中新发染色体异常对易位携带者胚胎诊断结果和临床结局的影响。方法对27个周期的罗氏易位和64个周期的相互易位携带者的囊胚采用二代测序(NGS)行PGD。结果罗氏易位和相互易位携带者的囊胚PGD结果显示,34.1%(139/408)的胚胎存在新发染色体异常;罗氏易位和相互易位各自的数据显示,罗氏易位携带者的完全新发染色体异常率为31.7%(40/126),数值上高于相互易位携带者的18.4%(52/282),但差异无统计学意义(P>0.05)。罗氏易位和相互易位携带者分别有70.4%(19/27)和54.7%(35/64)的PGD周期检出完全新发染色体异常囊胚;临床结局显示分别有7.4%(2/27)的罗氏易位PGD周期和18.8%(12/64)的相互易位PGD周期由于新发染色体异常导致无正常结果的胚胎可供移植。结论罗氏易位和相互易位携带者的囊胚PGD均不同程度的面临新发染色体异常的影响。相比于相互易位携带者,罗氏易位携带者中完全新发染色体异常的囊胚检出率更高,但由于罗氏易位携带者可用的正常或易位携带胚胎率更高,实际其PGD周期受到的影响要小于相互易位。
Objective:To evaluate the influence of de novo chromosomal abnormality on the preimplantation genetic diagnosis(PGD)and clinical outcome of Robertsonian and reciprocal translocation carriers.Methods:The next generation sequencing(NGS)was used for PGD in 27 cycles of Robertsonian translocation carriers and 64 cycles of reciprocal translocation carriers.Results:The PGD results from the blastocysts of Robertsonian and reciprocal translocation carriers showed that 34.1%(139/408)embryos had de novo chromosomal abnormality.The rate of complete de novo chromosomal abnormality in Robertsonian translocation carriers was 31.7%(40/126),which was higher than that in reciprocal translocation carriers[18.4%(52/282)],but there was no significant difference(P>0.05).The complete de novo chromosomal abnormality blastocysts were detected in 70.4%(19/27)PGD cycles of Robertsonian carriers and 54.7%(35/64)PGD cycles of reciprocal translocation carriers.Clinical outcomes showed that 7.4%(2/27)PGD cycles of Robertsonian translocation and 18.8%(12/64)PGD cycles of reciprocal translocation had no normal embryo for transplantation due to de novo chromosomal abnormality.Conclusions:The de novo chromosomal abnormality of blastocyst PGD of Robertsonian and reciprocal translocation carriers were in varying degrees.Compared with reciprocal translocation,there were more complete de novo chromosomal abnormalities in Robertsonian translocation blastocysts.However,due to the higher rate of normal or balanced translocation embryos available for Robertsonian translocation carriers,it was less affected for embryo transfer than reciprocal translocation.
Objective:To evaluate the influence of de novo chromosomal abnormality on the preimplantation genetic diagnosis(PGD)and clinical outcome of Robertsonian and reciprocal translocation carriers.Methods:The next generation sequencing(NGS)was used for PGD in 27 cycles of Robertsonian translocation carriers and 64 cycles of reciprocal translocation carriers.Results:The PGD results from the blastocysts of Robertsonian and reciprocal translocation carriers showed that 34.1%(139/408)embryos had de novo chromosomal abnormality.The rate of complete de novo chromosomal abnormality in Robertsonian translocation carriers was 31.7%(40/126),which was higher than that in reciprocal translocation carriers[18.4%(52/282)],but there was no significant difference(P>0.05).The complete de novo chromosomal abnormality blastocysts were detected in 70.4%(19/27)PGD cycles of Robertsonian carriers and 54.7%(35/64)PGD cycles of reciprocal translocation carriers.Clinical outcomes showed that 7.4%(2/27)PGD cycles of Robertsonian translocation and 18.8%(12/64)PGD cycles of reciprocal translocation had no normal embryo for transplantation due to de novo chromosomal abnormality.Conclusions:The de novo chromosomal abnormality of blastocyst PGD of Robertsonian and reciprocal translocation carriers were in varying degrees.Compared with reciprocal translocation,there were more complete de novo chromosomal abnormalities in Robertsonian translocation blastocysts.However,due to the higher rate of normal or balanced translocation embryos available for Robertsonian translocation carriers,it was less affected for embryo transfer than reciprocal translocation.
引文
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[14]Vanneste E,Voet T,Le CC,et al.Chromosome instability is common in human cleavage-stage embryos[J].Nat Med,2009,15:577-583.
[15]Guichaoua MR,Quack B,Speed RM,et al.Infertility in human males with autosomal translocations:meiotic study of a 14;22 Robertsonian translocation[J].Hum Genet,1990,86:162-166.
[16]Wang BT,Chong TP,Boyar FZ,et al.Abnormalities in spontaneous abortions detected by G-banding and chromosomal microarray analysis(CMA)at a national reference laboratory[J].Mol Cytogenet,2014,7:33.
[17]van Koningsbruggen S,Gierlinski M,Schofield P,et al.Highresolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli[J].Mol Biol Cell,2010,21:3735-3748.
[2]Munné S.Analysis of chromosome segregation during preimplantation genetic diagnosis in both male and female translocation heterozygotes[J].Cytogenet Genome Res,2005,111:305-309.
[3]Lejeune J.Autosomal disorders[J].Pediatrics,1963,32:326-337.
[4]Zhang W,Liu Y,Wang L,et al.Clinical application of nextgeneration sequencing in preimplantation genetic diagnosis cycles for Robertsonian and reciprocal translocations[J].JAssist Reprod Genet,2016,33:899-906.
[5]王玮,偶健,丁洁,等.应用荧光原位杂交对相互易位携带者进行植入前遗传学诊断[J].江苏医药,2012,38:1439-1441.
[6]Wells D,Kaur K,Grifo J,et al.Clinical utilisation of a rapid lowpass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation[J].J Med Genet,2014,51:553-562.
[7]Anton E,Vidal F,Blanco J.Reciprocal translocations:tracing their meiotic behavior[J].Genet Med,2008,10:730-738.
[8]Wang B,Nie B,Tang D,et al.Analysis of Meiotic segregation patterns and interchromosomal effects in sperm from 13Robertsonian translocations[J].Balkan J Med Genet,2017,20:43-50.
[9]Rogenhofer N,Dürl S,Ochsenkühn R,et al.Case report:elevated sperm aneuploidy levels in an infertile Robertsonian translocation t(21;21)carrier with possible interchromosomal effect[J].J Assist Reprod Genet,2012,29:343-346.
[10]Piomboni P,Stendardi A,Gambera L.Chromosomal aberrations and aneuploidies of spermatozoa[J].Adv Exp Med Biol,2014,791:27-52.
[11]Munné S,Escudero T,Fischer J,et al.Negligible interchromosomal effect in embryos of Robertsonian translocation carriers[J/OL].Reprod Biomed Online,2005,10:363-369.
[12]Kovaleva NV.Increased risk of trisomy 21in offspring of carriers of balanced non-contributing autosomal rearrangements is not explained by interchromosomal effect[J].Genetika,2013,49:259-268.
[13]Alfarawati S,Fragouli E,Colls P,et al.Embryos of robertsonian translocation carriers exhibit a mitotic interchromosomal effect that enhances genetic instability during early development[J/OL].PLoS Genet,2012,8:e1003025.
[14]Vanneste E,Voet T,Le CC,et al.Chromosome instability is common in human cleavage-stage embryos[J].Nat Med,2009,15:577-583.
[15]Guichaoua MR,Quack B,Speed RM,et al.Infertility in human males with autosomal translocations:meiotic study of a 14;22 Robertsonian translocation[J].Hum Genet,1990,86:162-166.
[16]Wang BT,Chong TP,Boyar FZ,et al.Abnormalities in spontaneous abortions detected by G-banding and chromosomal microarray analysis(CMA)at a national reference laboratory[J].Mol Cytogenet,2014,7:33.
[17]van Koningsbruggen S,Gierlinski M,Schofield P,et al.Highresolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli[J].Mol Biol Cell,2010,21:3735-3748.