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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (10): 68-73.doi: 10.6040/j.issn.1671-7554.0.2022.0398

• 临床医学 • 上一篇    下一篇

364例孕早中期自然流产组织单核苷酸多态性微阵列分析

高青,鲁婷,单珊,陶靖,金华   

  1. 山东第一医科大学附属济南市妇幼保健院产前诊断中心, 山东 济南 250001
  • 发布日期:2022-09-30
  • 通讯作者: 金华. E-mail:tonyshirly@163.com

Single nucleotide polymorphism microarray analysis of 364 cases of spontaneous abortion during early and middle pregnancy

GAO Qing, LU Ting, SHAN Shan, TAO jing, JIN Hua   

  1. Prenatal Diagnosis Center, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan 250001, Shandong, China
  • Published:2022-09-30

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摘要： 目的 探讨单核苷酸多态性微阵列分析技术在早中孕期自然流产中的应用。 方法 选取364例自然流产组织为研究对象,应用单核苷酸多态性微阵列分析技术回顾分析导致自然流产的染色体异常分布。分别按孕周、年龄、流产组织性别分组:孕6~12周组(n=300),孕13~28周组(n=64);孕妇年龄<35岁组(n=292),≥35岁组(n=72);男性组(n=147),女性组(n=217)。比较各组各类染色体异常发生率。 结果 在364例自然流产组织中,检出染色体异常 191例(52.47%)分别为:染色体数目异常177例;致病性染色体微重复微缺失11例;全染色体单亲二倍体3例,病理均为葡萄胎,来自父亲。孕6~12周组染色体数目异常发生率(55.33%)、三体发生率(37.00%)、单体发生率(8.33%)、三倍体发生率(6.00%)与孕6~12周组染色体数目异常发生率(17.19%)、三体发生率(9.38%)、单体发生率(3.13%)、三倍体发生率(0%)比较差异均有统计学意义(P<0.001;P<0.001;P=0.030;P=0.004)。孕13~28周仅检出18三体、21三体、45,XO及嵌合体共13例,占染色体数目异常7.34%(13/177)。孕妇年龄≥35岁组染色体数目异常发生率(63.88%)、三体发生率(51.39%)与<35岁组染色体数目异常发生率(44.86%)、三体发生率(27.40%)比较差异有统计学意义(P=0.048;P=0.005)。男性组与女性组染色体差异率比较差异无统计学意义(P=0.562)。 结论 孕早期、高龄孕妇自然流产组织染色体数目异常率更高;染色体异常是自然流产的主要原因;应用单核苷酸多态性微阵列分析技术能够检出其他方法无法检出的单亲二倍体。

关键词: 自然流产, 单核苷酸多态性微阵列, 染色体, 单亲二倍体

Abstract: Objective To investigate the application of single nucleotide polymorphism microarray(SNP array)in spontaneous abortion in early and middle pregnancy. Methods A total of 364 cases of spontaneous abortion were selected, and the distribution of chromosomal abnormalities leading to spontaneous abortion were analyzed with SNP array. The patients were divided into groups according to the gestational weeks, pregnant age and sex of abortion tissue, including gestational 6-12 weeks group(n=300)and gestational 13-28 weeks group(n=64); under 35 years old group(n=292)and over 35 years old group(n=72); male group(n=147), and female group(n=217). Results Of all 364 cases, 191(52.47%)presented chromosomal abnormalities, including 177 cases of abnormal chromosome number, 11 cases of microdeletion/microduplication, 3 cases of whole chromosome uniparental disomy(pathology revealed hydatidiform moles, paternal). In the gestational 6-12 weeks group, there were 55.33% cases with abnormal chromosome number, 37.00% with trisomy, 8.33% with monosomy, and 6.00% with triploid. In the gestational 13-28 weeks group, there were 17.19% cases with abnormal chromosome number, 9.38% with trisomy, 3.13% with monosomy, and 0% with triploid. There were significant differences between the two groups(P<0.001; P<0.001; P=0.030; P=0.004). In the over 35 years old group, there were 63.88% cases with abnormal chromosome number, and 51.39% with trisomy. In the under 35 years old group, there were 44.86% with abnormal chromosome number, and 27.40% with trisomy. The abnormal rate was significantly higher in the over 35 years group(P=0.048; P=0.005). However, there was no significant difference in the number of chromosome aberration between male and female abortion tissue(P=0.562). Conclusion The rate of chromosomal abnormality is higher in early pregnancy and women with advanced age. Chromosomal abnormality is the main cause of spontaneous abortion. The application of SNP array can detect uniparental diploid that cannot be detected by other methods.

Key words: Spontaneous abortion, Single nucleotide polymorphism microarray analysis, Chromosome, Uniparental diploid

中图分类号: 

  • R714.21
[1] Wu T, Yin B, Zhu Y, et a1. Mo1ecular cytogenetic analysis of early spontaneous abortions conceived from varying assisted reproductive technology procedures [J]. Mol Cytogenet, 2016, 9: 79. doi: 10.1186/s13039-016-0284-2.
[2] Arias-Sosa LA, Acosta ID, Lucena-Quevedo E, et a1. Genetic and epigenetic variations associated with idiopathic recurrent pregnancy1oss [J]. J Assist Reprod Genet, 2018, 35(3): 355-366.
[3] Qu S, Wang L, Cai A, et a1. Exploring the cause of early miscarriage with SNP-array analysis and karyotyping [J]. Matern Fetal Neonatal Med, 2019, 32(1): 1-10.
[4] 朱丽芬, 张慧敏, 杜绮婷, 等. 应用单核苷酸多态性微阵列分析早、中孕期流产的遗传学因素[J]. 中华医学遗传学杂志, 2022, 39(6): 576-580. ZHU Lifen, ZHANG Huimin, DU Qiting, et al. Comprehensive genetic analysis in first or second trimester pregnancy losusing chromosomal microarray with single nucleotide polymorphism probes [J]. Chinese Journal of Medical Genetics, 2022, 39(9): 576-580.
[5] 肖艳华, 时盼盼, 李鼎, 等. 染色体微阵列技术在自然流产或死胎原因分析中的应用 [J]. 中华医学遗传学杂志, 2020, 37(4): 389-391. XIAO Yanhua, SHI Panpan, LI Ding, et al. Chromosomal microarray analysis for the causes of miscarriage or still birth [J]. Chinese Journal of Medical Genetics, 2020, 37(4): 389-391.
[6] 王菊, 刘娜, 周玉侠, 等. 基因芯片技术在早期自然流产遗传学诊断中的应用研究[J]. 中国优生与遗传杂志, 2019, 27(3): 312-313. WANG Ju, LIU Na, ZHOU Yuxia, et al. The application of gene chip technology in the genetic diagnosis of early spontaneous abortion [J]. Chinese Journal of Birth Health & Heredity, 2019, 27(3): 312-313.
[7] 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.
[8] Smits MAJ, van Maarle M, Hamer G, et al. Cytogenetic testing of pregnancy loss tissue:a meta-analysis [J]. Reprod Biomed Online, 2020, 40(6): 867-879.
[9] Gou L, Liu T, Wang Y, et a1. C1inica1 uti1ization of chromosoma1 microarray ana1ysis for the genetic ana1ysis in subgroups of pregnancy1os [J]. J Matern Fetal Neonata1 Med, 2020, 23: 1-8. doi: 10. 1080/14767058. 2020. 1849126.
[10] 张华, 杨黎明, 袁路, 等. 高通量测序在孕早期自然流产中的应用[J]. 中国医学工程, 2020, 28(10): 10-14. ZHANG Hua, YANG Liming, YUAN Lu, et al. Application of high throughput sequencing in early spontaneous abortion [J]. China Medical Engineering, 2020, 28(10): 10-14.
[11] van den Berg MM, van Maarle MC, van Wely M, et al. Genetics of early miscarriage [J]. Biochim Biophys Acta, 2012, 1822(12): 1951-1959.
[12] Huang Y, Tu M, Qian Y, et al. Age-dependent metabolomic profile of the follicular fluids from women undergoing assisted reproductive technology treatment [J]. Front Endocrinol(Lausanne), 2022, 13: 818888. doi: 10.3389/ fendo. 2022. 818888.
[13] Ma JY, Li S, Chen LN, et al. Why is oocyte aneuploidy increased with maternal aging? [J]. Genet Genomics, 2020, 47(11): 659-671.
[14] Jaslow CR, Carney JL, Kutteh WH, et al. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses [J]. Fertil Steril, 2010, 93(4): 1234-1243.
[15] 赵燕, 曹鲁泉, 刘真真, 等. 245例自然流产组织染色体异常分析[J]. 中华围产医学杂志, 2019, 22(5): 331-335. ZHAOYan, CAO Luquan, LIU Zhenzhen, et al. Chromosome abnormalities in 245 cases of spontaneous abortion [J]. Chinese Journal of Perinatal Medicine, 2019, 22(5): 331-335.
[16] Grati FR, Gallazzi G, Branca L, et al. An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening [J]. Reprod BioMed Online, 2018, 36(4): 442-449.
[17] Nadesapillai S, van der Velden J, Smeets D, et al. Why are some patients with 45, X Turner syndrome fertile? A young girl with classical 45, X Turner syndrome and a cryptic mosaicism in the ovary [J]. Fertil Steril, 2021, 115(5): 1280-1287.
[18] Dai R, Li L, Zhu H, et al. Effect of maternal age on spontaneous abortion during the first trimester in Northeast China [J]. Matern Fetal Neonatal Med, 2018, 31(14): 1824-1829.
[19] Lalou I, Gkrozou F, Meridis E, et a1. Mo1ecu1ar investigation of uniparenta1disomy(UPD)in spontaneous abortions [J]. Eur J Obstet Gynecol Reprod Bio1, 2019, 236: 116-120. doi: 10.1016/j.ejogrb.2019.03.004.
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