Prenatal diagnosis result analysis of 884 fetuses with sex chromosomal abnormalities

doi:10.3969/j.issn.1673-8640.2024.02.009

Abstract

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

CLC Number:

R446.7

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.

Figures/Tables 3

References 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)