高通量测序遗传学筛查对性染色体非整倍体患者的应用价值
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摘要
目的探讨新一代高通量测序植入前遗传学筛查(NGS-PGS)对于性染色体非整倍体患者的应用价值。方法观察组采用新一代高通量测序(NGS)技术对8例性染色体非整倍体(SCA)患者的囊胚进行了全部23对染色体的筛查,取同期因反复流产行植入前遗传学筛查的21例患者作为对照组,比较两组患者的临床资料。结果两组女性患者的年龄、平均获卵数、MII率、受精率、卵裂率和可利用囊胚形成率间差异均无统计学意义(均P>0. 05);两组患者囊胚的染色体非整倍体率间比较差异无统计学意义(37. 5%vs. 40. 6%; P>0. 05)。在SCA患者检测的24个囊胚中,未发现性染色体异常,9个异常的囊胚均为常染色体的非整倍体。结论 SCA患者囊胚中性染色体异常比例很低,并不需要专门针对性染色体进行检测,但鉴于其较高的常染色体非整倍体发生率,仍有必要进行PGS,以减低流产率和防止出生缺陷。
Objective Explore the application value of a new generation of high-throughput sequencing preimplantation genetic screening( NGS-PGS) for patients with aneuploidy of sex chromosomes( SCA). Methods A total of 23 pairs of chromosomes were screened for blastocysts of 8 patients with aneuploidy using a new generation of high-throughput sequencing technology. 21 patients with preimplantation genetic screening for recurrent miscarriage were taken at the same time. The patient served as a control and compared the clinical data of the two groups of patients. Results There was no statistically significant difference in age,mean eggs number,MII rate,fertilization rate,cleavage rate and available blastocyst formation rate between the two groups( P>0. 05); There was no statistical difference between aneuploidy rates( 37. 5% vs 40. 6%; P>0. 05). Among the 24 blastocysts detected in patients with sex aneuploidy,no sex chromosome abnormalities were found,and 9 abnormal blastocysts were autosomal aneuploidy. Conclusion The proportion of abnormalities in the blastocyst of the SCA of patients with sex chromosomes is very low and does not need to be specifically tested for sex chromosomes. However,due to its high incidence of autosomal aneuploidy,PGS is still necessary to reduce the miscarriage rate and prevent birth defects.
Objective Explore the application value of a new generation of high-throughput sequencing preimplantation genetic screening( NGS-PGS) for patients with aneuploidy of sex chromosomes( SCA). Methods A total of 23 pairs of chromosomes were screened for blastocysts of 8 patients with aneuploidy using a new generation of high-throughput sequencing technology. 21 patients with preimplantation genetic screening for recurrent miscarriage were taken at the same time. The patient served as a control and compared the clinical data of the two groups of patients. Results There was no statistically significant difference in age,mean eggs number,MII rate,fertilization rate,cleavage rate and available blastocyst formation rate between the two groups( P>0. 05); There was no statistical difference between aneuploidy rates( 37. 5% vs 40. 6%; P>0. 05). Among the 24 blastocysts detected in patients with sex aneuploidy,no sex chromosome abnormalities were found,and 9 abnormal blastocysts were autosomal aneuploidy. Conclusion The proportion of abnormalities in the blastocyst of the SCA of patients with sex chromosomes is very low and does not need to be specifically tested for sex chromosomes. However,due to its high incidence of autosomal aneuploidy,PGS is still necessary to reduce the miscarriage rate and prevent birth defects.
引文
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[2] Nagy B,Nagy RG,Lazar L,et al. Detection of sex chromosome aneuploidies using quantitative fluorescent PCR in the Hungarian population[J]. Clin Chim Acta,2015,445(1):2-6.
[3] Nicolaides KH,Musci TJ,Struble CA,et al. Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA analysis[J].Fetal Diagn Ther,2014,35(1):1-6.
[4] Tartaglia NR,Wilson R,Miller JS,et al. Autism Spectrum Disorder in Males with Sex Chromosome Aneuploidy:XXY/Klinefelter Syndrome,XYY,and XXYY[J]. J Dev Behav Pediatr,2017,38(3):197-207.
[5] Krausz C,Casamonti E. Spermatogenic failure and the Y chromosome[J]. Hum Genet,2017,136(5):637-655.
[6] Lanfranco F1,Kamischke A,Zitzmann M,et al. Klinefelter's syndrome[J]. Lancet,2004,364(9430):273-283.
[7] Mao JM,Zhao LM,Hong K,et al. Microdissection testicular sperm extraction for patients with nonmosaic Klinefelter syndrome:A report of 143 cases[J]. Zhong hua Nan Ke Xue,2017,23(12):1075-1079.
[8] Wu EX,Wilson AD,Wong EC,et al. Maternal origin of 47,XXY and confined placental mosaicism 47,XXY/48,XXY,+13 in an infant conceived through IVF[J]. J Assist Reprod Genet,2013,30(6):807-812.
[9] Goldschmidt E1,Márquez M,Solari A,et al. Phenotypic variability in 47,XXX patients:Clinical report of four new cases[J]. Arch Argent Pediatr,2010,108(4):e88-e91.
[10] Le Gall J,Nizon M,Pichon O,et al. Sex chromosome aneuploidies and copy-number variants:a further explanation for neurodevelopmental prognosis variability[J]? Eur J Hum Genet,2017,25(8):930-934.
[11] Altunyurt S1,Acar B,Guclu S,et al. Mosaic form(45X/46XX)of Turner's syndrome. A case report[J]. J Reprod Med,2002,47(12):1053-1054.
[12] Franciscolvarez-Nava,Roberto Lanes. Epigenetics in Turner syndrome[J]. Clin Epigenetics,2018,10(1):45.
[13] Milazzo JP,Rives N,Mousset-Siméon N,et al. Chromosome constitution and apoptosis of immature germ cells present in sperm of two47,XYY infertile males[J]. Hum Reprod,2006,21(7):1749-1758.
[14] Fullerton G,Hamilton M,Maheshwari A. Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?[J].Hum Reprod,2010,25(3):588-597.
[15] Staessen C,Tournaye H,Van Assche E,et al. PGD in 47,XXY Klinefelter's syndrome patients[J]. Hum Reprod Update,2003,9(4):319-330.