CNV-seq联合STR分型技术在早期自然流产物遗传学分析中的应用

doi:10.3969/j.issn.1673-8640.2026.02.003

摘要/Abstract

摘要：

目的探讨基因组拷贝数变异测序（CNV-seq）和短串联重复序列（STR）分型联合检测在早期自然流产遗传学病因分析中的价值。方法选取2022年1月—2023年12月连云港市妇幼保健院自然流产患者529例。收集所有患者的流产物组织样本，采用CNV-Seq联合STR分型检测染色体拷贝数变异（CNV）情况，对染色体非整倍体和>100 kb的CNV进行分析。对提示D、G组染色体和大片段CNV异常的流产物组织的生物学父母进行外周血G显带染色体核型分析。结果 529例自然流产患者的流产物组织样本中检出322例染色体异常，其中染色体数目异常279例（染色体非整倍体异常240例、三倍体39例）、CNV异常43例（亚显微CNV 11例、大片段CNV 32例）。复发性CNV样本中有3例15q11.2微缺失综合征和2例16p11.2微缺失综合征均为家族性遗传，且父母均无明显临床表型。外周血染色体核型分析检出染色体平衡易位携带者6例、染色体罗氏易位携带者2例。结论 CNV-seq联合STR分型检测可排除母源污染，检出三倍体异常，提高遗传学病因自然流产的整体检出率。对检出胚胎染色体存在D、G组非整倍体和大片段CNV异常的样本进行父母外周血染色体核型分析可以及时发现染色体平衡易位，为流产后临床管理和再生育提供指导，避免再次自然流产。

关键词: 拷贝数变异测序, 短串联重复序列, 核型分析, 拷贝数变异, 早期自然流产

Abstract:

Objective To investigate the role of genomic copy number variation sequencing（CNV-seq） combined with short tandem repeat（STR） typing in the genetic etiology of early spontaneous abortion. Methods A total of 529 patients with spontaneous abortion in Lianyungang Maternal and Child Health Hospital from January 2022 to December 2023 were enrolled. All the patients' products of abortion tissue samples were collected，and CNV-seq combined with STR typing was used to determine chromosomal copy number variation（CNV）. Chromosomal aneuploidy and CNV >100 kb were analyzed. Peripheral blood G-banding karyotype analysis was performed on the biological parents of the products of abortion tissue samples with abnormal D and G group chromosomes and large CNV. Results Among the 529 products of abortion tissue samples from patients with spontaneous abortion，322 cases of chromosomal abnormalities were determined，including 279 cases of chromosomal number abnormalities（240 cases of chromosomal aneuploidy and 39 cases of chromosomal triploidy） and 43 cases of CNV abnormalities（11 cases of submicroscopic CNV and 32 cases of large CNV）. Among the recurrent CNV，3 cases of 15q11.2 microdeletion syndrome and 2 cases of 16p11.2 microdeletion syndrome were inherited from fathers or mothers with no obvious clinical phenotypes. Peripheral blood karyotype analysis detected 6 cases of chromosomal balanced translocation carriers and 2 cases of chromosomal Robertsonian translocation carriers. Conclusions The combination of CNV-seq and STR typing can eliminate maternal contamination and detect triploidy abnormalities，which can better improve the overall detection rate of genetic etiology in spontaneous abortion. For the products of abortion tissue samples with D and G group aneuploidy and large CNV abnormalities，peripheral blood karyotype analysis of parents can timely detect chromosomal balanced translocations，providing timely guidance for precise clinical management and subsequent reproduction after spontaneous abortion and avoiding recurrent spontaneous abortion.

Key words: Copy number variation sequencing, Short tandem repeat technology, Karyotype analysis, Copy number variation, Early spontaneous abortion

中图分类号:

R446.7

金培芹, 许阳, 熊英巧, 彭新秀. CNV-seq联合STR分型技术在早期自然流产物遗传学分析中的应用[J]. 检验医学, 2026, 41(2): 112-117.

JIN Peiqin, XU Yang, XIONG Yingqiao, PENG Xinxiu. Application of CNV-seq combined with STR typing technology in genetic analysis of early spontaneous abortion products[J]. Laboratory Medicine, 2026, 41(2): 112-117.

图/表 4

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类型	例数	百分比/%
非整倍体	240	45.4
染色体三体	199	37.6
累及1条染色体	186	35.2
累及2条染色体	12	2.3
累及3条染色体	1	0.1
染色体单体	41	7.8
常染色体	4	0.8
性染色体	37	7.0
多倍体（三倍体）	39	7.4
合计	279	100.0

类型	例数	百分比/%
非整倍体	240	45.4
染色体三体	199	37.6
累及1条染色体	186	35.2
累及2条染色体	12	2.3
累及3条染色体	1	0.1
染色体单体	41	7.8
常染色体	4	0.8
性染色体	37	7.0
多倍体（三倍体）	39	7.4
合计	279	100.0

嵌合类型	具体变异	检出例数/例	嵌合比例/%
染色体三体		5	45.8±17.9
累及1条染色体	arr[hg19]（12）×3	1	25.0
	arr[hg19]（5）×2-3	1	35.0
	arr[hg19]（15）×2-3	1	64.0
	arr[hg19]（3）×2-3	1	40.0
累及2条染色体	arr[hg19]（9）×2-3 arr[hg19]（21）×2-3	1	65.0 65.0
染色体单体		3	61.7±17.2
性染色体	45，XO	1	46.0
	45，XO	1	59.0
	45，XO	1	80.0

嵌合类型	具体变异	检出例数/例	嵌合比例/%
染色体三体		5	45.8±17.9
累及1条染色体	arr[hg19]（12）×3	1	25.0
	arr[hg19]（5）×2-3	1	35.0
	arr[hg19]（15）×2-3	1	64.0
	arr[hg19]（3）×2-3	1	40.0
累及2条染色体	arr[hg19]（9）×2-3 arr[hg19]（21）×2-3	1	65.0 65.0
染色体单体		3	61.7±17.2
性染色体	45，XO	1	46.0
	45，XO	1	59.0
	45，XO	1	80.0

病例	CNV-seq	片段大小	致病基因	相关综合征和临床表型
1	15q13.3（31999631-32444043） x1	444 kb	CHRNA7	15q13微缺失综合征；癫痫、特发性全面性癫痫、自闭症等
2	1p36.33p36.32（849466-2925858） x1	2.08 Mb	GABRD、SAMD11、NOC2L、PERM1等43个基因	lp36微缺失综合征；智力障碍，面部畸形
3	15q11.2（22770421-23191761） x1	421 kb	TUBGCP5、CYFIP1、NIPA2、NIPA1	智力障碍，自闭症等
4	15q11.2（22770422-23214339）x1	444 kb	TUBGCP5、CYFIP1、NIPA2、NIPA1	智力障碍，自闭症等
5	15q11.2（22770422-23276605）x1	506 kb	TUBGCP5、CYFIP1、NIPA2、NIPA1	智力障碍，自闭症等
6	16p11.2（29591326-30176508） x1	585 kb	TBX6、PRRT2、PAGR1、MVP等20个基因	智力障碍，自闭症，癫痫等
7	16p11.2（29567297-30178406）x1	611 kb	TBX6、PRRT2、PAGR1、MVP 等22个基因	智力障碍，自闭症，癫痫等
8	2p12p11.2（77886659-87313256） x1	9.43 Mb	REG3G、CTNNA2、LRRTM1、SUCLG1等37个基因	2p11.2-p12微缺失综合征；发育迟缓、智力障碍、面部异常、耳朵异常、骨骼和生殖器畸形等
9	22q13.32q13.33（49179545-51197766） x1	2.02 Mb	SHANK3、ACR、BRD1、ZBED4等29个基因	22q13.3缺失综合征（Phelan-McDermid综合征）；发育迟缓，中度至深度智力障碍，肌张力降低及言语缺失或延迟
10	1p36.33p36.31（849467-6698503）x1	5.85 Mb	CHD5、GNB1、GABRD、SAMD11等72个基因	lp36微缺失综合征；智力障碍，面部畸形等
11	16p13.11（14892976-16538596） x1	1.36 Mb	MYH11、NOMO1、NPIPA1、PDXDC1等11个基因	16p13.11微缺失综合征；癫痫、智力障碍、多发畸形、自闭症等