Clinical value of non-invasive prenatal testing for screening of fetal chromosome copy number variation

doi:10.3877/cma.j.issn.1673-5250.2022.03.008

Objective

To explore clinical value of non-invasive prenatal testing (NIPT) for screening of fetal chromosome copy number variation (CNV), mainly microdeletion/microduplication.

Methods

From January 2019 to October 2021, a total of 67 pregnant women whose results of NIPT showed fetal chromosomes deletions or repetitive abnormal in First Hospital of Shanxi Medical University, and then received interventional prenatal diagnosis, were selected as research subjects. Their clinical data were retrospectively analyzed. Fetal chromosome karyotype analysis and chromosome microarray analysis (CMA) were performed on amniotic fluid cells of pregnant women to analyze the consistency of fetal chromosome CNV between NIPT and interventional prenatal diagnosis. The procedure of this study was consistent with the Helsinki Declaration of World Medical Association revised in 2013. All pregnant women gave their informed consent to the above mentioned tests and sign the informed consent forms.

Results

① During above time period, there were 29 479 pregnant women who received NIPT and 87 cases showed abnormal of deletion or duplication of fetal chromosomes, and rate of fetal chromosome CNV was 0.30%(87/29 479). ② There were 35 cases diagnosed as fetal chromosomal CNV among 67 pregnant women who received interventional prenatal diagnosis, and the positive predictive value of NIPT screening for fetal chromosomal CNV was 52.2%(35/67). Among 67 pregnant women, 29 cases of CMA results of fetal chromosomal CNV were coincident with NIPT, and coincident rate of fetal chromosomal CNV detected by NIPT and CMA was 43.2%(29/67).

Conclusions

It is feasible of NIPT screening for fetal chromosome CNV. For those who have fetal chromosome CNV results of NIPT, prenatal diagnosis should be further taken to confirm the diagnosis.

Key words: Chromosomes, Noninvasive prenatal testing, DNA copy number variations, Prenatal diagnosis, Microdeletion, Microduplication, Microarray analysis, Pregnant women

表1 35例确诊为染色体CNV胎儿的NIPT及产前诊断结果比较

病例(No.)	NIPT结果	染色体核型分析结果	CMA结果	CNV分类
1	del(1q)，4.8 Mb	46，XN	del(1)(q43)，3.4 Mb	pCNV
2	del(1p)，3.08 Mb	46，XN	del(1)(p36.33 p36.32)，1.9 Mb	pCNV
3	20号染色体偏多	46，XN	del(1)(q21.3)，117.4 kb	良性CNV
4	dup(2q), 12.3 Mb	46，XN，add(2)(q34)	dup(2)(q34 q37.3)，33.4 Mb	均为pCNV
			dup(14)(q11.2q12)，5.4 Mb
5	del(2q12.12)，1.49 Mb	46，XN	del(2)(q21.1)，320.1 kb	临床意义不明确CNV
6	dup(4q)，5.5 Mb	46，XN	dup(3)(q21.2)，786.5 kb	均为pCNV
			dup(4)(q12)，3.9 Mb
7	3号染色体部分缺失	46，XN	del(3)(q25.32 q26.31)，14.8 Mb杂合性缺失	均为临床意义不明确CNV
8	del(4q), 9.96 Mb	46，XN，del(4)(q35)	del(4)(q34.3q35.2)，11.7 Mb	均为pCNV
			dup(3)(p26.3p26.)，3.8 Mb
9	dup(5q)，1.02 Mb	46，XN	dup(5)(q11.2)，809.0 kb	pCNV
10	dup(14q)，5.75 Mb	46，XN	dup(14)(q24.3q31.1)，1.3 Mb 2次重复	均为pCNV
11	22号染色体偏多	46，XN	dup(7)(p12.1p11.2)，4.3 Mb	pCNV
12	dup(7q)，4.91 Mb	46，XN	dup(7)(q36.3)，2.1 Mb	pCNV
			del(9)(p24.2)，115.7 kb	良性CNV
13	del(X)(q21.1-q28)，25.29Mb	46，XN	dup(8)(p21.2)，1.2 Mb	良性CNV
14	dup(8p)，5.38 Mb	46，XN	dup(8)(p23.2p23.1)，2.6 Mb	临床意义不明确CNV
15	del(9p)，15.05 Mb	46，XN，del(9)(p24)	del(9)(p24.3p23)，13.6 Mb	pCNV
16	10号染色体异常	46，XN，dup(10)(q26)	dup(10)(p15.3p12.1)，25.9 Mb	均为pCNV
			dup(10)(q26.13q26.2)，2.5 Mb
			del(10)(q26.2q26.3)，6.3 Mb
17	del(12p)，1.5 Mb	46，XN	del(12)(p11.23)510.1 kb	pCNV
18	del(12q)，6.8 Mb	46，XN	del(12)(q24.32q24.33)，4.2 Mb	pCNV
19	del(1p)，32.99 Mb	46，XN	dup(12)(q24.21)，250.1 kb	临床意义不明确CNV
20	del(13q)，18.51 Mb	46，XN，del(13)(q14)	del(2)(q21.1)，320.1 kb	均为pCNV
			del(13)(q21.2q21.33)，11.6 Mb
			del(13)(q21.33q31.1)，8.9 Mb
			del(20)(p12.3p12.2)，1.3 Mb
21	del(14q)，8.76 Mb	46，XN	del(14)(q13.3q21.2)，7.7 Mb	pCNV
22	del(14q) ，21.5 Mb	46，XN，del(14)(q32)	del(14)(q32.11q32.33)，17.2 Mb杂合性缺失	均为pCNV
23	性染色体偏多	45，X(12)/46，XN(88)	疑似有低比例45，X/46，XX，或XXX/X/XX，或XXX/X等性染色体嵌合del(15)(q15.2)，329.0 kb	均为pCNV
24	del(15)(q11.2-q13.1)，5.43 Mb	46，XN	del(15)(q11.2q13.1)，6.2 Mb	pCNV
25	11号染色体偏多	46，XN	dup(16)(p13.11)，1.6 Mb	pCNV
26	22号染色体偏多	46，XN	del(16)(p11.2)，946.9 kb	临床意义不明确CNV
27	15号染色体偏多	47，XN，+15(8)/ 46，XN(62)	胎儿疑似为低比例15号染色体三体嵌合体	临床意义不明确CNV
28	dup(17q)，3.5 Mb	46，XN	dup(17)(q12)，1.8 Mb	pCNV
29	dup(18p)，25.8 Mb	46，XY，der(18)t(18；21)？	dup(18)(p11.32q12.1)，31.2 Mb	pCNV
30	18-三体高风险	46，XN，+add(18)？	dup(18)(q11.1q12.1)，9.5 Mb	临床意义不明确CNV
31	del(18q22.2-q23)，10.33 Mb	46，XN，18？	dup(18)(p11.32p11.22)，9.6 Mb	均为pCNV
			del(18)(q22.2q23)，11.1 Mb
32	del(15q)，5.14 Mb	46，XN	del(15)(q21.3q22.2)，4.8 Mb	pCNV
33	del(21q)，9.05 Mb	46，XN	del(21)(q22.12q22.3)，11.3 Mb杂合性缺失	均为pCNV
34	20号染色体偏多	47，XN，+20(58)/ 46，XN(12)	2条20号染色体分别来自父母一方的单亲二体性	pCNV
35	dup(22q)，5.61 Mb	46，XN	dup(22)(q11.21q11.23)，3.5 Mb	pCNV

表1 35例确诊为染色体CNV胎儿的NIPT及产前诊断结果比较

病例(No.)	NIPT结果	染色体核型分析结果	CMA结果	CNV分类
1	del(1q)，4.8 Mb	46，XN	del(1)(q43)，3.4 Mb	pCNV
2	del(1p)，3.08 Mb	46，XN	del(1)(p36.33 p36.32)，1.9 Mb	pCNV
3	20号染色体偏多	46，XN	del(1)(q21.3)，117.4 kb	良性CNV
4	dup(2q), 12.3 Mb	46，XN，add(2)(q34)	dup(2)(q34 q37.3)，33.4 Mb	均为pCNV
			dup(14)(q11.2q12)，5.4 Mb
5	del(2q12.12)，1.49 Mb	46，XN	del(2)(q21.1)，320.1 kb	临床意义不明确CNV
6	dup(4q)，5.5 Mb	46，XN	dup(3)(q21.2)，786.5 kb	均为pCNV
			dup(4)(q12)，3.9 Mb
7	3号染色体部分缺失	46，XN	del(3)(q25.32 q26.31)，14.8 Mb杂合性缺失	均为临床意义不明确CNV
8	del(4q), 9.96 Mb	46，XN，del(4)(q35)	del(4)(q34.3q35.2)，11.7 Mb	均为pCNV
			dup(3)(p26.3p26.)，3.8 Mb
9	dup(5q)，1.02 Mb	46，XN	dup(5)(q11.2)，809.0 kb	pCNV
10	dup(14q)，5.75 Mb	46，XN	dup(14)(q24.3q31.1)，1.3 Mb 2次重复	均为pCNV
11	22号染色体偏多	46，XN	dup(7)(p12.1p11.2)，4.3 Mb	pCNV
12	dup(7q)，4.91 Mb	46，XN	dup(7)(q36.3)，2.1 Mb	pCNV
			del(9)(p24.2)，115.7 kb	良性CNV
13	del(X)(q21.1-q28)，25.29Mb	46，XN	dup(8)(p21.2)，1.2 Mb	良性CNV
14	dup(8p)，5.38 Mb	46，XN	dup(8)(p23.2p23.1)，2.6 Mb	临床意义不明确CNV
15	del(9p)，15.05 Mb	46，XN，del(9)(p24)	del(9)(p24.3p23)，13.6 Mb	pCNV
16	10号染色体异常	46，XN，dup(10)(q26)	dup(10)(p15.3p12.1)，25.9 Mb	均为pCNV
			dup(10)(q26.13q26.2)，2.5 Mb
			del(10)(q26.2q26.3)，6.3 Mb
17	del(12p)，1.5 Mb	46，XN	del(12)(p11.23)510.1 kb	pCNV
18	del(12q)，6.8 Mb	46，XN	del(12)(q24.32q24.33)，4.2 Mb	pCNV
19	del(1p)，32.99 Mb	46，XN	dup(12)(q24.21)，250.1 kb	临床意义不明确CNV
20	del(13q)，18.51 Mb	46，XN，del(13)(q14)	del(2)(q21.1)，320.1 kb	均为pCNV
			del(13)(q21.2q21.33)，11.6 Mb
			del(13)(q21.33q31.1)，8.9 Mb
			del(20)(p12.3p12.2)，1.3 Mb
21	del(14q)，8.76 Mb	46，XN	del(14)(q13.3q21.2)，7.7 Mb	pCNV
22	del(14q) ，21.5 Mb	46，XN，del(14)(q32)	del(14)(q32.11q32.33)，17.2 Mb杂合性缺失	均为pCNV
23	性染色体偏多	45，X(12)/46，XN(88)	疑似有低比例45，X/46，XX，或XXX/X/XX，或XXX/X等性染色体嵌合del(15)(q15.2)，329.0 kb	均为pCNV
24	del(15)(q11.2-q13.1)，5.43 Mb	46，XN	del(15)(q11.2q13.1)，6.2 Mb	pCNV
25	11号染色体偏多	46，XN	dup(16)(p13.11)，1.6 Mb	pCNV
26	22号染色体偏多	46，XN	del(16)(p11.2)，946.9 kb	临床意义不明确CNV
27	15号染色体偏多	47，XN，+15(8)/ 46，XN(62)	胎儿疑似为低比例15号染色体三体嵌合体	临床意义不明确CNV
28	dup(17q)，3.5 Mb	46，XN	dup(17)(q12)，1.8 Mb	pCNV
29	dup(18p)，25.8 Mb	46，XY，der(18)t(18；21)？	dup(18)(p11.32q12.1)，31.2 Mb	pCNV
30	18-三体高风险	46，XN，+add(18)？	dup(18)(q11.1q12.1)，9.5 Mb	临床意义不明确CNV
31	del(18q22.2-q23)，10.33 Mb	46，XN，18？	dup(18)(p11.32p11.22)，9.6 Mb	均为pCNV
			del(18)(q22.2q23)，11.1 Mb
32	del(15q)，5.14 Mb	46，XN	del(15)(q21.3q22.2)，4.8 Mb	pCNV
33	del(21q)，9.05 Mb	46，XN	del(21)(q22.12q22.3)，11.3 Mb杂合性缺失	均为pCNV
34	20号染色体偏多	47，XN，+20(58)/ 46，XN(12)	2条20号染色体分别来自父母一方的单亲二体性	pCNV
35	dup(22q)，5.61 Mb	46，XN	dup(22)(q11.21q11.23)，3.5 Mb	pCNV

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