改良高分辨G显带技术在复杂染色体重排携带者中的应用
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摘要
目的应用染色体改良高分辨G显带技术,对四例复杂染色体重排(CCRs)携带者进行细胞遗传学分析,探讨该技术对CCRs的临床应用价值。方法选取因复发性流产或不孕不育就诊于广东省妇幼保健院医学遗传中心的4对夫妇,经改良高分辨G显带技术制备外周血染色体,核型分析并与常规方法进行比较。结果改良高分辨G显带染色体分辨率达到550条以上核型占比50%以上;核型分析提示4对夫妇中各有一方是CCRs携带者,涉及3～4条染色体易位;易位染色体涉及3号和12号染色体最多。结论改良高分辨G显带技术能更好的发现CCRs携带者的多个染色体易位,避免漏诊。该技术成本较低、操作简单,适合在基层单位推广。
Objective To investigate the cytogenetic analysis of 4 patients with complex chromosomal rearrangements(CCRs)by using chromosome modified high resolution G banding technique,and explore the clinical value of this technique in CCRs. Methods The karyotype of peripheral blood chromosomes was prepared from 4 couples referring for recurrent abortion or infertility in the Medical Genetic Center of Guangdong Women and Children Hospital. The karyotype of peripheral blood was prepared by improved high resolution G banding technique and compared with conventional methods. Results The resolution of the modified high resolution G banding chromosomes was over 50%,and the karyotype analysis showed that one of each couple was CCRs carriers,which involved 3 or 4 chromosome translocations. The most involving chromosomes were 3 and 12. Conclusion Improved high resolution G banding technique can better detect multiple chromosome translocations and avoid missed diagnosis in CCRs carriers. The technology is simple in operation and low cost,and is suitable for promotion in grassroots units.
Objective To investigate the cytogenetic analysis of 4 patients with complex chromosomal rearrangements(CCRs)by using chromosome modified high resolution G banding technique,and explore the clinical value of this technique in CCRs. Methods The karyotype of peripheral blood chromosomes was prepared from 4 couples referring for recurrent abortion or infertility in the Medical Genetic Center of Guangdong Women and Children Hospital. The karyotype of peripheral blood was prepared by improved high resolution G banding technique and compared with conventional methods. Results The resolution of the modified high resolution G banding chromosomes was over 50%,and the karyotype analysis showed that one of each couple was CCRs carriers,which involved 3 or 4 chromosome translocations. The most involving chromosomes were 3 and 12. Conclusion Improved high resolution G banding technique can better detect multiple chromosome translocations and avoid missed diagnosis in CCRs carriers. The technology is simple in operation and low cost,and is suitable for promotion in grassroots units.
引文
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[6]吴菁,尹爱华,傅文婷,等.改进同步化法制备外周血染色体500条G显带技术的临床应用研究[J].中华医学遗传学杂志,2013,30(3):377-378.
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[8]Poot M,Haaf T.Mechanisms of origin,phenotypic effects and diagnostic implications of complex chromosome rearrangements[J].Mol Syndromol,2015,6(3):110-134.
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[10]廖亚平,王春景,梁猛,等.平衡复杂染色体重排携带者的遗传与生育情况分析[J].遗传,2017,39(5):396-412.
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[14]Patsalis PC.Complex chromosomal rearrangements[J].Genet Couns,2007,18(1):57-69.
[15]Kausch K,Haaf T,K?hler J,et al.Complex chromosomal rearrangement in a woman with multiple miscarriages[J].Am JMed Genet,1988,31(2):415-420.
[16]Kousseff BG,Papenhausen P,Essig YP,et al.Complex chromosome rearrangement with ankyloblepharon filiforme adnatum[J].J Med Genet,1993,30(2):167-170.
[17]Giardino D,Corti C,Ballarati L,et al.Prenatal diagnosis of a de novo complex chromosome rearrangement(CCR)mediated by six breakpoints,and a review of 20 prenatally ascertained CCRs[J].Prenat Diagn,2006,26(6):565-570.
[18]Martin RH.Cytogenetic determinants of male fertility[J].Hum Reprod Update,2008,14(4):379-390.
[19]Vermeulen S,Menten B,Van Roy N,et al.Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations:delineation of7q21.11 breakpoints[J].Am J Med Genet A,2004,124A(1):10-18.
[20]Zhang Y,Dai Y,Tu Z,et al.Array-CGH detection of three cryptic submicroscopic imbalances in a complex chromosome rearrangement[J].J Genet,2009,88(3):369-372.
[21]林欣怡,宋新明,李颖,等.染色体微小易位致智力障碍家系的遗传学研究[J].热带医学杂志,2018,18(5):574-577,602.
[22]Schluth-Bolard C,Labalme A,Cordier MP,et al.Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations[J].J Med Genet,2013,50(3):144-150.
[23]Aristidou C,Koufaris C,Theodosiou A,et al.Accurate breakpoint mapping in apparently balanced translocation families with discordant phenotypes using whole genome mate-pair sequencing[J].PLoS One,2017,12(1):e0169935.
[2]Nguyen MH,Morel F,Pennamen P,et al.Balanced complex chromosome rearrangement in male infertility:case report and literature review[J].Andrologia,2015,47(2):178-185.
[3]Alesi V,Orlando V,Genovese S,et al.Interstitial 10q21.1q23.31duplication due to meiotic recombination of a paternal balanced complex rearrangement:cytogenetic and molecular characterization[J].Cytogenet Genome Res,2017,151(4):179-185.
[4]de Pagter MS,van Roosmalen MJ,Baas AF,et al.Chromothripsis in healthy individuals affects multiple proteincoding genes and can result in severe congenital abnormalities in offspring[J].Am J Hum Genet,2015,96(4):651-656.
[5]Pellestor F,Anahory T,Lefort G,et al.Complex chromosomal rearrangements:origin and meiotic behavior[J].Hum Reprod Update,2011,17(4):476-494.
[6]吴菁,尹爱华,傅文婷,等.改进同步化法制备外周血染色体500条G显带技术的临床应用研究[J].中华医学遗传学杂志,2013,30(3):377-378.
[7]Yunis JJ.High resolution of human chromosomes[J].Science,1976,191(4233):1268-1270.
[8]Poot M,Haaf T.Mechanisms of origin,phenotypic effects and diagnostic implications of complex chromosome rearrangements[J].Mol Syndromol,2015,6(3):110-134.
[9]Aristidou C,Theodosiou A,Ketoni A,et al.Cryptic breakpoint identified by whole-genome mate-pair sequencing in a rare paternally inherited complex chromosomal rearrangement[J].Mol Cytogenet,2018,11:34.
[10]廖亚平,王春景,梁猛,等.平衡复杂染色体重排携带者的遗传与生育情况分析[J].遗传,2017,39(5):396-412.
[11]Zhang T,Sun Y,Chen Z,et al.Traditional and molecular chromosomal abnormality analysis of products of conception in spontaneous and recurrent miscarriage[J].BJOG,2018,125(4):414-420.
[12]Tsai AG,Lieber MR.Mechanisms of chromosomal rearrangement in the human genome[J].BMC Genomics,2010,11 Suppl 1:S1.
[13]De Gregori M,Ciccone R,Magini P,et al.Cryptic deletions are a common finding in“balanced”reciprocal and complex chromosome rearrangements:a study of 59 patients[J].J Med Genet,2007,44(12):750-762.
[14]Patsalis PC.Complex chromosomal rearrangements[J].Genet Couns,2007,18(1):57-69.
[15]Kausch K,Haaf T,K?hler J,et al.Complex chromosomal rearrangement in a woman with multiple miscarriages[J].Am JMed Genet,1988,31(2):415-420.
[16]Kousseff BG,Papenhausen P,Essig YP,et al.Complex chromosome rearrangement with ankyloblepharon filiforme adnatum[J].J Med Genet,1993,30(2):167-170.
[17]Giardino D,Corti C,Ballarati L,et al.Prenatal diagnosis of a de novo complex chromosome rearrangement(CCR)mediated by six breakpoints,and a review of 20 prenatally ascertained CCRs[J].Prenat Diagn,2006,26(6):565-570.
[18]Martin RH.Cytogenetic determinants of male fertility[J].Hum Reprod Update,2008,14(4):379-390.
[19]Vermeulen S,Menten B,Van Roy N,et al.Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations:delineation of7q21.11 breakpoints[J].Am J Med Genet A,2004,124A(1):10-18.
[20]Zhang Y,Dai Y,Tu Z,et al.Array-CGH detection of three cryptic submicroscopic imbalances in a complex chromosome rearrangement[J].J Genet,2009,88(3):369-372.
[21]林欣怡,宋新明,李颖,等.染色体微小易位致智力障碍家系的遗传学研究[J].热带医学杂志,2018,18(5):574-577,602.
[22]Schluth-Bolard C,Labalme A,Cordier MP,et al.Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations[J].J Med Genet,2013,50(3):144-150.
[23]Aristidou C,Koufaris C,Theodosiou A,et al.Accurate breakpoint mapping in apparently balanced translocation families with discordant phenotypes using whole genome mate-pair sequencing[J].PLoS One,2017,12(1):e0169935.