胎儿心内强回声光点与染色体异常及预后关联性的研究

王娣; 汪菁

doi:10.16766/j.cnki.issn.1674-4152.003750

胎儿心内强回声光点与染色体异常及预后关联性的研究

doi: 10.16766/j.cnki.issn.1674-4152.003750

王娣¹,
汪菁^{1, 2, ,}

1.
蚌埠医科大学研究生院，安徽蚌埠 233030
2.
安徽省立医院妇产科产前诊断中心，安徽合肥 230001

基金项目:

安徽省重点研究与开发计划项目 202004j07020024

详细信息

通讯作者:
汪菁，E-mail：ahwangjing1968@126.com

中图分类号: R445.1 R714.5
计量
- 文章访问数: 22
- HTML全文浏览量: 11
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2023-10-10
- 网络出版日期: 2024-12-31

A study on the relationship between intracardiac hyperechogenic focus and chromosomal abnormality and prognosis

WANG Di¹,
WANG Jing^{1, 2
, ,}

1.
Graduate School of Bengbu Medical University, Bengbu, Anhui 233030, China

摘要

摘要: 目的探讨胎儿心内强回声光点(intracardiac hyperechogenic focus，ICEF)与遗传性染色体异常间的关联程度，并分析ICEF对胎儿预后评估的影响。方法采用回顾性研究方法, 分析2019年1月—2022年12月于安徽省立医院进行产前超声诊断的ICEF单胎妊娠病例450例，采集胎儿羊水或脐带血标本，利用核型分析及拷贝数变异测序(copy number variation sequencing，CNV-seq)技术对标本进行遗传学检测，记录相关检测结果及妊娠结局。结果本研究检出核型异常14例，检出CNV致病性变异15例。核型分析联合CNV-seq检测后，孤立性胎儿心内强回声光点组染色体异常检出例数(2例，9.5%)较非孤立性组染色体异常检出例数(19例，90.5%)低，差异有统计学意义(χ²=7.282，P=0.007)。以孤立性心内强回声光点为对照组，当ICEF合并颈项透明层(nuchal translucency，NT)增厚时，其染色体异常检出3例(χ²=28.362，P＜0.001)，当ICEF合并胎儿心内结构异常时，其染色体异常检出7例(χ²=7.492，P=0.005)。当ICEF合并NT增厚或胎儿心内结构异常时，其染色体异常的概率显著增加(P＜0.05)。结论核型分析与CNV-seq检测的联合应用在提高ICEF胎儿染色体异常检出率方面具有重要价值，非孤立性胎儿心内强回声光点病例中染色体异常的检出率更高，提示在临床实践中需给予更多关注。
- 心内强回声光点 /
- 基因组疾病 /
- 超声软指标 /
- 核型分析 /
- 拷贝数变异测序
Abstract: Objective To investigate the degree of association between intracardiac hyperechogenic focus (ICEF) and genetic chromosomal abnormalities, and to discuss the implications of assessing fetal prognosis. Methods A retrospective study design was used to analyze 450 cases of intracardiac hyperechogenic focus singleton pregnancy diagnosed by prenatal ultrasound in Anhui Provincial Hospital from January 2019 to December 2022. By collecting fetal amniotic fluid or umbilical cord blood samples, karyotype analysis and copy number variation sequencing (CNV-seq) techniques were used to perform genetic testing of the specimens, and associated test results and pregnancy outcomes were recorded. Results In this study, 14 cases of abnormal karyotype and 15 cases of pathogenic variation of CNV were detected. After karyotype analysis combined with CNV-seq detection, the number of chromosome abnormalities detected in the isolated intracardiac hyperechogenic focus group (2 cases, 9.5%) was lower than that in the non-isolated intracardiac hyperechogenic focus group (19 cases, 90.5%), and the difference was statistically significant (χ²=7.282, P=0.007). Isolated intracardiac hyperechogenic focus was used as control group, the number of chromosomal abnormalities was detected when ICEF was combined with Nuchal Translucency (NT) thickening (3 cases, χ²=28.362, P < 0.001), the number of chromosomal abnormalities was detected when ICEF was combined with fetal cardiac structural abnormalities (7 cases, χ²=7.492, P=0.005). The probability of chromosomal abnormality was significantly increased when ICEF was combined with NT thickening or fetal cardiac structural abnormalities (P < 0.05). Conclusion The combined application of karyotype analysis and CNV-seq detection has an important value in improving the detection rate of chromosomal abnormalities in intracardiac hyperechogenic focus. The detection rate of chromosomal abnormalities in non-isolated intracardiac hyperechogenic focus is higher, suggesting that it should be given more attention in clinical practice.
- Intracardiac hyperechogenic focus /
- Genomic disease /
- Ultrasound soft markers /
- Karyotyping /
- Copy number variation sequencing

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表 1 15例异常CNV测序结果的临床意义及妊娠结局

Table 1. Clinical significance and pregnancy outcomes in 15 cases with abnormal CNV-seq results

年龄(岁)	孕周(周)	染色体核型分析	CNV测序结果	临床意义	结局
33	28	46，XN	46，XN，dup(22q11.21)(18, 765, 311-21, 630, 621)×3	致病	引产
26	29	47，XN+21	47，XN+21.seq[GRCh37/hg19](21)×3	致病	引产
39	26	47，XN+21	T21	致病	引产
28	24	46，X？del(x)del(Xq24q26.2)	46, XN, del(Xq24q26.2).(q24q26)seq[GRCh37/hg19](117, 582, 516-131, 175, 640)×1	致病	存活
29	23	46，XN	46, XN, dup(Xp22.12).seq[GRCh37/hg19](19, 937, 983-20, 376, 497)×2	致病	存活
33	19	45，X, t(1;10) (q12;p11, 1)	45, XO.seq[GRCh37/hg19](1-22)×2, (X)×1	致病	存活
22	23	46，XN	seq[GRCh37]dup(15q11.2q13.1) 15q11-q13(22.58M-28.5M)chr15:g.21885000-29030451dup	致病	引产
24	22	46，XN	seq[GRCh37]dup(16p11.2p11.2)chr16:g.29436431-30306324dup	致病	引产
33	25	46，XN	seq[GRCh37]del(2q13q13)chr2:g.111174154-113172512del	致病	存活
37	25	48，XXNN	seq[GRCh37]dup(Xp22.33q28)chrX: g.1-155270560dup seq[GRCh37]dup(Yp11.32q12)chrY: g.1-59373566dup	致病	引产
28	22	46，XN	seq[GRCh37]dup(17q12q12)chr17:g.34555614-36299170dup	致病	引产
44	22	47，XN+21	T21	致病	引产
34	19	47，XN+21	T21	致病	引产
41	25	46，XN	seq[GRCh37]del(8q24.3q24.3)chr8:g.144755907-145615849del	致病	引产
37	18	47，XN+21	T21	致病	引产

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表 2 染色体核型分析联合CNV-Seq检测胎儿染色体异常的检出率[例(%)]

Table 2. Detection rate of fetal chromosomal abnormalities via combined chromosome karyotype analysis and CNV-Seq[cases (%)]

组别	例数	染色体异常(n=21)	χ²值	P值	核型异常(n=14)	χ²值	P值	CNV异常(n=15)	χ²值	P值
ICEF			7.282	0.007		4.120	0. 042		3.820	0.009
孤立性	168	2(9.5)			1(7.1)			2(13.3)
非孤立性	282	19(90.5)			13(92.9)			13(86.7)
孕周			4.532	0.033		11.572	0. 001		1.255	0.263
≥28周	39	5(23.8)			5(35.7)			3(20.0)
＜28周	411	16(76.2)			9(64.3)			12(80.0)
孕母年龄			20.478	＜0.001		32.336	0. 001		9.251	0.002
＜35岁	397	12(57.1)			5(35.7)			9(60.0)
≥35岁	53	9(42.9)			9(64.3)			6(40.0)
强光点			0.058	0.810		2.056	0.152		＜0.001	0.999
单心室	366	18(85.7)			14(100.0)			12(80.0)
双心室	84	3(14.3)			0			3(20.0)

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表 3 孤立性ICEF与非孤立性ICEF染色体及心超异常概况(例)

Table 3. Overview of chromosome and cardiac abnormality in isolated ICEF and non-isolated ICEF (cases)

组别	例数	染色体异常	χ²值	P值	核型异常	χ²值	P值	CNV异常	χ²值	P值	胎儿心超异常	χ²值	P值
孤立性ICEF	168	2			1			2			20
ICEF合并心外结构异常	180	3	＜0.001	0.999^a	3	0.188	0.664^a	2	＜0.001	0.999^a	24	0.161	0.689^a
ICEF合并心内结构异常	75	7	7.492	0.005^a	5	5.616	0.018^a	6	5.564	0.018^a	34	33.524	＜0.001^a
ICEF合并多个软指标异常	138	6	1.856	0.173^a	4	1.273	0.259^a	6	1.856	0.173^a	26	2.853	0.091^a
注：^a为与孤立性ICEF进行比较。

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表 4 孤立性ICEF与非孤立性ICEF染色体异常情况比较(例)

Table 4. Chromosome abnormalities in isolated ICEF and non-isolated ICEF (cases)

组别	例数	染色体异常	χ²值	P值	核型异常	χ²值	P值	CNV异常	χ²值	P值
孤立性ICEF	168	2			1			2
ICEF合并NT≥2.5 mm	7	3	28.362	＜0.001^a	3	36.482	＜0.001^a	3	28.362	＜0.001^a
ICEF合并鼻骨发育不良	23	1	0.062	0.321^a	1	0.320	0.277^a	1	0.062	0.321^a
ICEF合并肠回声增强	37	0			0			0
ICEF合并三尖瓣反流	30	2	4.927	0.026^a	1		0.281^a	1	0.005	0.391^a
注：^a为与孤立性ICEF进行比较。

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