884例性染色体异常胎儿产前诊断结果分析

doi:10.3969/j.issn.1673-8640.2024.02.009

检验医学 ›› 2024, Vol. 39 ›› Issue (2): 149-154.DOI: 10.3969/j.issn.1673-8640.2024.02.009

• 基因组技术与罕见病、遗传病诊治专题 • 上一篇下一篇

884例性染色体异常胎儿产前诊断结果分析

杨微微¹, 姚立英², 任晨春¹(), 王文靖¹, 张海霞¹, 李雯², 李博³

1.天津市中心妇产科医院南开大学附属妇产医院检验科，天津 300100
2.天津市中心妇产科医院南开大学附属妇产医院产前诊断中心，天津 300100
3.天津医科大学研究生院，天津 300070

收稿日期:2023-07-12 修回日期:2023-11-01 出版日期:2024-02-28 发布日期:2024-03-26
通讯作者: 任晨春
作者简介:任晨春，E-mail：rccxqy@163.com。
杨微微，女，1985年生，硕士，主管技师，主要从事细胞遗传学检验工作。
基金资助:
天津市卫生健康委员会科技项目(zc20117);天津市科技计划项目(21JCQNJC01860);天津市医学重点学科(专科)建设项目(妇产科学TJYXZDXK-043A)

Prenatal diagnosis result analysis of 884 fetuses with sex chromosomal abnormalities

YANG Weiwei¹, YAO Liying², REN Chenchun¹(), WANG Wenjing¹, ZHANG Haixia¹, LI Wen², LI Bo³

1. Department of Clinical Laboratory，Tianjin Central Hospital of Gynecology and Obstetrics，Nankai University Maternity Hospital，Tianjin 300100，China
2. Department of Prenatal Diagnosis，Tianjin Central Hospital of Gynecology and Obstetrics，Nankai University Maternity Hospital，Tianjin 300100，China
3. Graduate School of Tianjin Medical University，Tianjin 300070，China

Received:2023-07-12 Revised:2023-11-01 Online:2024-02-28 Published:2024-03-26
Contact: REN Chenchun

摘要/Abstract

摘要：

目的对884例无创产前筛查(NIPS)提示性染色体异常的羊水样本进行核型分析、荧光原位杂交技术(FISH)和拷贝数变异测序(CNV-seq)检测，探讨不同方法在产前诊断中的价值。方法选取2015年1月—2022年12月天津市中心妇产科医院孕早期NIPS提示胎儿为性染色体异常的孕妇884例，于孕中期采集羊水样本，进行羊水细胞核型分析和FISH检测，对结果不一致或培养失败的样本进一步行CNV-seq检测。结果 884例孕妇中，有341例(38.6%)检出异常核型，11例(1.2%)羊水细胞培养失败。NIPS性染色体阳性预测值为39.2%(341/873)。341例核型分析异常样本中，最常见的核型异常类型是47，XXY(108例)，其次为47，XXX(80例)、47，XYY(68例)、45，X(18例)，共检出51例嵌合体。884例孕妇中，有862例FISH检测结果与核型分析或CNV-seq结果一致，FISH的阳性预测值为97.5%；24例与核型分析结果不一致，进一步行CNV-seq检测，有22例CNV-seq结果与核型分析结果一致，并能相互补充分析；2例不一致样本中，1例核型分析结果为46，+mar，FISH和CNV-seq结果均为45，X；1例核型分析结果为嵌合Y染色体异染色质区缺失，FISH和CNV-seq结果均为嵌合体，结构未见异常。结论 NIPS提示性染色体异常时，建议首选FISH和核型分析联合检测，可快速、准确地诊断染色体异常。对于疑似染色体特殊结构异常，建议进行FISH、核型分析和CNV-seq联合检测，可明确遗传学病因。

关键词: 无创产前筛查, 染色体核型分析, 荧光原位杂交技术, 拷贝数变异测序, 性染色体异常, 产前诊断

Abstract:

Objective To perform karyotype analysis，fluorescence in situ hybridization(FISH) and copy number variation sequencing(CNV-seq) on 884 amniotic fluid samples with non-invasive prenatal screening(NIPS) sex chromosomal abnormalities，and to investigate the roles of different methods in prenatal diagnosis. Methods A total of 884 patients who received NIPS in the first trimester of pregnancy and indicated that the fetus was with sex chromosomal abnormality were enrolled from Tianjin Central Hospital of Gynecology and Obstetrics from January 2015 to December 2022. Amniotic fluid samples were collected in the second trimester of pregnancy，and karyotype analysis and FISH were performed. CNV-seq was further performed on the samples with inconsistent results or culture failure. Results In the 884 cases，341 cases(38.6%) of abnormal karyotype were determined，amniotic fluid cell culture failed in 11 cases(1.2%)，and the positive predictive value was 39.2%(341/873). Among the 341 fetuses with abnormal karyotype analysis，the most common abnormal type was 47，XXY(108 cases)，followed by 47，XXX(80 cases) and 47，XYY(68 cases). Totally，18 cases were 45，X. Totally，51 cases were determined as chimera. The results of FISH in 862 cases(862/884) were consistent with those of karyotype analysis or CNV-seq，and the positive predictive value of FISH was 97.5%. A total of 24 cases were different from karyotype analysis，and CNV-seq was performed further. In the 22 cases，the results of CNV-seq were consistent with those of karyotype analysis，which could complement each other. The karyotype of 1 of the 2 inconsistent samples was 46，+mar，and the results of FISH and CNV-seq were 45，X. The karyotype analysis of 1 case showed that the heterochromatin region of chimeric Y chromosome was missing，the results of FISH and CNV-seq were chimeric，and the structure was not abnormal. Conclusions Combined determination of FISH and karyotype analysis is recommended when NIPS indicates chromosomal abnormalities，which can quickly and accurately diagnose chromosomal abnormalities. For suspected special structural abnormalities of chromosomes，FISH，karyotype analysis and CNV-seq combined determination is recommended to identify the genetic cause.

Key words: Non-invasive prenatal screening, Chromosome karyotype analysis, Fluorescence in situ hybridization, Copy number variation sequencing, Sex chromosomal abnormality, Prenatal diagnosis

中图分类号:

R446.7

杨微微, 姚立英, 任晨春, 王文靖, 张海霞, 李雯, 李博. 884例性染色体异常胎儿产前诊断结果分析[J]. 检验医学, 2024, 39(2): 149-154.

YANG Weiwei, YAO Liying, REN Chenchun, WANG Wenjing, ZHANG Haixia, LI Wen, LI Bo. Prenatal diagnosis result analysis of 884 fetuses with sex chromosomal abnormalities[J]. Laboratory Medicine, 2024, 39(2): 149-154.

图/表 3

参考文献 23

[1]	NIELSEN J, WOHLERT M. Chromosome abnormalities found among 34 910 newborn children:results from a 13-year incidence study in Arhus,Denmark[J]. Hum Genet, 1991, 87(1):81-83. DOI URL
[2]	RIGGS E R, ANDERSEN E F, CHERRY A M, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics(ACMG) and the Clinical Genome Resource(ClinGen)[J]. Genet Med, 2020, 22(2):245-257.
[3]	余昳, 吕嬿. 2022年ACMG胎儿染色体异常无创产前筛查实践指南解读[J]. 实用妇产科杂志, 2023, 39(8):583-586.
[4]	BAYINDIR B, DEHASPE L, BRISON N, et al. Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management[J]. Eur J Hum Genet, 2015, 23(10):1286-1293. DOI PMID
[5]	WANG Y, CHEN Y, TIAN F, et al. Maternal mosaicism is a significant contributor to discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing[J]. Clin Chem, 2014, 60(1):251-259. DOI PMID
[6]	YU T, LI S, ZHAO W, et al. False positive non-invasive prenatal testing results due to vanishing twins[J]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2019, 36(4):327-330.
[7]	WANG J W, LYU Y N, QIAO B, et al. Cell-free fetal DNA testing and its correlation with prenatal indications[J]. BMC Pregnancy and Childbirth, 2021, 21(1):585. DOI
[8]	谢成秀. 羊水染色体核型的遗传效应分析[J]. 医学信息, 2018, 31(10):80-83.
[9]	《男性生殖遗传学检查专家共识》编写组, 中华医学会男科学分会. 男性生殖遗传学检查专家共识[J]. 中华男科学杂志, 2015, 21(12):1138-1142.
[10]	李朋, 白刚, 孟凯, 等. 克氏综合征早期筛查诊断与不育症治疗策略[J]. 中华生殖与避孕杂志, 2021, 41(10):943-947.
[11]	吴斌. 21例Turner综合征细胞遗传学临床分析[J]. 中国优生与遗传杂志, 2015, 23(11) :58-59.
[12]	SAN ROMAN A K, PAGE D C. A strategic research alliance:turner syndrome and sex differences[J]. Am J Med Genet C Semin Med Genet, 2019, 181(1):59-67.
[13]	CERNAT A, DE FREITAS C, MAJID U, et al. Facilitating informed choice about non-invasive prenatal testing(NIPT):a systematic review and qualitative meta-synthesis of women's experiences[J]. BMC Pregnancy Childbirth, 2019, 19(1):27. DOI
[14]	PÖS O, BUDIŠ J, SZEMES T. Recent trends in prenatal genetic screening and testing[J]. F1000Res, 2019, 8: F1000 Faculty Rev-764.
[15]	中国医院协会临床检验专业委员会出生缺陷防控实验技术与管理学组, 刘世国, 王敬丽, 等. 产前荧光原位杂交技术专家共识[J]. 中华医学遗传学杂志, 2020, 37(9):918-923.
[16]	中华预防医学会出生缺陷预防与控制专业委员会, 中国优生科学协会基因诊断与精准医学分会, 胡婷, 等. 拷贝数变异检测在产前诊断中的应用指南[J]. 中华医学遗传学杂志, 2020, 37(9):909-917.
[17]	马慧英, 刘淑敏, 彭措吉, 等. 荧光原位杂交技术及染色体核型分析在产前诊断中的应用[J]. 检验医学, 2017, 32(8):730-732. DOI
[18]	中华预防医学会出生缺陷预防与控制专业委员会, 中国优生科学协会基因诊断与精准医学分会, 胡婷, 等. 拷贝数变异检测在产前诊断中的应用指南[J]. 中华医学遗传学杂志, 2020, 37(9):909-917.
[19]	汪菁, 徐晶晶, 陈玲, 等. CNV-Seq在高龄孕妇产前诊断中的应用[J]. 安徽医科大学学报, 2019, 54(10):1659-1662.
[20]	刘淑敏, 彭措吉, 张世宽, 等. CNV-seq和染色体核型分析联合检测在高原地区产前诊断中的应用[J]. 高原医学杂志, 2020, 30(4):37-41.
[21]	TOUTAIN J, EPINEY M, BEGORRE M. First-trimester prenatal diagnosis performed on pregnant women with fetal ultrasound abnormalities:the reliability of interphase fluorescence in situ hybridization(FISH)on mesenchymal core for the main aneuploidies[J]. Eur J Obstet Gynecol Reprod Biol, 2010, 149(2):143-146. DOI URL
[22]	WANG H, WANG T, YANG N, et al. The clinical analysis of small supernumerary marker chromosomes in 17 children with mos 45,X/46,X,+mar karyotype[J]. Oncol Lett, 2017, 13(6):4385-4389. DOI PMID
[23]	MATSUBARA K, YANAGIDA K, NAGAI T, et al. De novo small supernumerary marker chromosomes arising from partial trisomy rescue[J]. Front Genet, 2020, 11:132. DOI URL

类别	例数	异常核型构成比/%	总异常发生率^①/%
47，XXY	108	31.68	12.37
47，XXX	80	23.46	9.16
47，XYY	68	19.94	7.79
45，X	18	5.28	2.07
48，XXXX	1	0.29	0.12
48，XXXY	1	0.29	0.12
46，X，+mar	1	0.29	0.12
del(X)	7	2.05	0.81
i(X)	5	1.47	0.57
46，Y，der(X)	1	0.29	0.12
嵌合体	51	14.96	5.85
合计	341	100.00	39.10

类别	例数	异常核型构成比/%	总异常发生率^①/%
47，XXY	108	31.68	12.37
47，XXX	80	23.46	9.16
47，XYY	68	19.94	7.79
45，X	18	5.28	2.07
48，XXXX	1	0.29	0.12
48，XXXY	1	0.29	0.12
46，X，+mar	1	0.29	0.12
del(X)	7	2.05	0.81
i(X)	5	1.47	0.57
46，Y，der(X)	1	0.29	0.12
嵌合体	51	14.96	5.85
合计	341	100.00	39.10

编号	孕妇年龄/岁	FISH	核型分析	CNV-seq
1	22	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
2	22	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
3	32	正常	46，X，del(X)(q26)	seq[GRCh37]del(X)(q26.1q28)
4	34	45，X[39]/46，XX[61]	46，X，i(X)(q10)[17]/45，X[13]	seq[GRCh37]X(p22.33p11.1)1，X(q11.1q28)2.2
5	26	45，X[30]/46，XX[70]	46，X，del(X)(p21)，22pstk+[28]/45，X，22pstk+[10]	seq[GRCh37]X(p22.33p21.1)1，X(p21.1q28)1.7
6	23	正常	46，X，i(X)(q10)[21]/46，XX[29]	seq[GRCh37] X (p22.33p11.1)1， X (q11.1q28)2
7	40	正常	46，X，del(X)(q21)	seq[GRCh37]del(X)(q21.1q28)
8	25	45，X[70]/46，XX[30]	46，X，i(X)(q10)[13]/45，X[10]	seq[GRCh37] X (p22.33p11.1)1， X (q11.1q28)1.6
9	34	45，X[49]/46，XX[51]	45，X[21]/46，X，i(Xq)[13]	seq[GRCh37] X (p22.33p11.1)1， X (q11.1q28)2
10	31	45，X[33]/46，XX[67]	45，X[25]/46，X，r(X)[7]	seq[GRCh37]X(p22.33q28)1，r(X)(p22.33q28)0.7
11	26	45，X[39]/46，XX[61]	46，X，del(X)(q21)[13]/45，X[3]	seq[GRCh37]X(p22.33q21.1)1.6， X(q21.1q28)1
12	29	45，X	46，X，+mar	seq[GRCh37]X(p22.33q28)*1
13	33	45，X[53]/46，XX[47]	46，X， del(X)(q11)[16]/45，X[14]	seq[GRCh37]X(p22.33p11.1)1.5，X(q11.1q28)1
14	27	45，X[14]/46，XY[86]	46，X，del(Y)(q12)[36]/45，X[26]	seq[GRCh37]X(p22.33q28)1，Y(p11.32q11.23)0.9
15	25	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
16	32	正常	46，X，del(X)(q26)	seq[GRCh37]del(X)(q26.2q28)
17	26	正常	46，X，del(X)(p21)	seq[GRCh37]del(X)(p22.33p21.2)
18	30	正常	46，Y，der(X)(dupYq)ins(X;Y)(p22.3;q11.21q11.223)	seq[GRCh37]dup(Y)(q11.21q11.223)
19	26	45，X[56]/46，XX[44]	45，X[19]/46，X，del(X)(p11.2)[16]	seq[GRCh37]X(p22.33p11.2)1，X(p11.2q28)1.5
20	30	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
21	32	正常	46，X，del(X)(p11)	seq[GRCh37]del(X)(p22.33p11.23)
22	25	45，X[68]/46，XX[32]	46，X，dup(X)(p22)[22]/45，X[20]	seq[GRCh37]del(X)(p22.33p11.22)0.78， del(X)(p11.22q28)0.22
23	30	正常	46，Y， i(X)(q10)	seq[GRCh37]X(p22.33p11.1)0， X (q11.1q28)2，Y(p11.32q11.23)*1
24	26	正常	46，X，del(X)(p21)	seq[GRCh37]del(X)(p22.33p21.2)

编号	孕妇年龄/岁	FISH	核型分析	CNV-seq
1	22	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
2	22	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
3	32	正常	46，X，del(X)(q26)	seq[GRCh37]del(X)(q26.1q28)
4	34	45，X[39]/46，XX[61]	46，X，i(X)(q10)[17]/45，X[13]	seq[GRCh37]X(p22.33p11.1)1，X(q11.1q28)2.2
5	26	45，X[30]/46，XX[70]	46，X，del(X)(p21)，22pstk+[28]/45，X，22pstk+[10]	seq[GRCh37]X(p22.33p21.1)1，X(p21.1q28)1.7
6	23	正常	46，X，i(X)(q10)[21]/46，XX[29]	seq[GRCh37] X (p22.33p11.1)1， X (q11.1q28)2
7	40	正常	46，X，del(X)(q21)	seq[GRCh37]del(X)(q21.1q28)
8	25	45，X[70]/46，XX[30]	46，X，i(X)(q10)[13]/45，X[10]	seq[GRCh37] X (p22.33p11.1)1， X (q11.1q28)1.6
9	34	45，X[49]/46，XX[51]	45，X[21]/46，X，i(Xq)[13]	seq[GRCh37] X (p22.33p11.1)1， X (q11.1q28)2
10	31	45，X[33]/46，XX[67]	45，X[25]/46，X，r(X)[7]	seq[GRCh37]X(p22.33q28)1，r(X)(p22.33q28)0.7
11	26	45，X[39]/46，XX[61]	46，X，del(X)(q21)[13]/45，X[3]	seq[GRCh37]X(p22.33q21.1)1.6， X(q21.1q28)1
12	29	45，X	46，X，+mar	seq[GRCh37]X(p22.33q28)*1
13	33	45，X[53]/46，XX[47]	46，X， del(X)(q11)[16]/45，X[14]	seq[GRCh37]X(p22.33p11.1)1.5，X(q11.1q28)1
14	27	45，X[14]/46，XY[86]	46，X，del(Y)(q12)[36]/45，X[26]	seq[GRCh37]X(p22.33q28)1，Y(p11.32q11.23)0.9
15	25	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
16	32	正常	46，X，del(X)(q26)	seq[GRCh37]del(X)(q26.2q28)
17	26	正常	46，X，del(X)(p21)	seq[GRCh37]del(X)(p22.33p21.2)
18	30	正常	46，Y，der(X)(dupYq)ins(X;Y)(p22.3;q11.21q11.223)	seq[GRCh37]dup(Y)(q11.21q11.223)
19	26	45，X[56]/46，XX[44]	45，X[19]/46，X，del(X)(p11.2)[16]	seq[GRCh37]X(p22.33p11.2)1，X(p11.2q28)1.5
20	30	正常	46，X，i(X)(q10)	seq[GRCh37]del(X)(p22.33p11.1)，dup(X)(q11.1q28)
21	32	正常	46，X，del(X)(p11)	seq[GRCh37]del(X)(p22.33p11.23)
22	25	45，X[68]/46，XX[32]	46，X，dup(X)(p22)[22]/45，X[20]	seq[GRCh37]del(X)(p22.33p11.22)0.78， del(X)(p11.22q28)0.22
23	30	正常	46，Y， i(X)(q10)	seq[GRCh37]X(p22.33p11.1)0， X (q11.1q28)2，Y(p11.32q11.23)*1
24	26	正常	46，X，del(X)(p21)	seq[GRCh37]del(X)(p22.33p21.2)

884例性染色体异常胎儿产前诊断结果分析

Prenatal diagnosis result analysis of 884 fetuses with sex chromosomal abnormalities

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[5]	孙恒娟, 杜成坎, 李红, 柳敏, 张泓. 细胞遗传学检测方法对MLL基因异常儿童急性白血病的诊断意义[J]. 检验医学, 2022, 37(12): 1196-1199.
[6]	赵旭亮, 田瑞霞, 施友文, 俞敏, 焦鎏鎏, 朱复希. 全外显子家系测序在WDR35基因复合杂合变异导致SRPS-5胎儿产前诊断中的价值[J]. 检验医学, 2022, 37(10): 928-933.
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[8]	孙恒娟, 杜成坎, 蒋慧, 邵静波, 李红, 张泓. 细胞遗传学技术在儿童急性白血病诊断中的应用价值[J]. 检验医学, 2021, 36(10): 1087-1089.
[9]	靳春雷, 朱焕勉, 陈鹏龙, 雷强. MYO15A基因新发突变导致先天性耳聋1例报道[J]. 检验医学, 2021, 36(10): 1090-1093.
[10]	余夏, 石明芳, 王双杰, 周元圆, 梁秀云. 91例同型地中海贫血基因携带者产前基因检测结果分析[J]. 检验医学, 2019, 34(3): 240-243.
[11]	马慧英, 刘淑敏, 彭措吉, 杨小萍. 荧光原位杂交技术及染色体核型分析在产前诊断中的应用[J]. 检验医学, 2017, 32(8): 730-732.
[12]	杜满兴, 王伟佳, 苏年华, 卢建强. 2 018例孕中期胎儿染色体核型分析结果回顾性分析[J]. 检验医学, 2016, 31(9): 778-781.
[13]	赵慧佳, 顾志冬, 程蔚蔚, 陶炯, 高佳琪, 韩旭. 上海地区汉族人群STR位点的选择和优化[J]. 检验医学, 2016, 31(9): 787-791.
[14]	鲍芸, 肖艳群, 王华梁. 高通量测序技术在无创产前筛查中的临床应用及研究进展[J]. 检验医学, 2016, 31(6): 541-545.
[15]	彭友帆, 刘洋, 张朝霞. 荧光原位杂交技术可早期有效的预测慢性粒细胞性白血病的预后[J]. 检验医学, 2015, 30(2): 167-172.

检测方法	结果正常	结果异常	不能出报告
FISH	24	11	0
核型分析	0	24	11
CNV-seq	11	24	0

检测方法	结果正常	结果异常	不能出报告
FISH	24	11	0
核型分析	0	24	11
CNV-seq	11	24	0