基因组测序技术在产前诊断中的应用

doi:10.3877/cma.j.issn.1673-5250.2026.04.002

中华妇幼临床医学杂志(电子版) ›› 2026, Vol. 22 ›› Issue (04) : 283 -289. doi: 10.3877/cma.j.issn.1673-5250.2026.04.002

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基因组测序技术在产前诊断中的应用

朱雨捷¹^,²^,³, 史蒙蒙¹^,²^,⁴, 贾春澍⁵, 曹也¹^,²^,⁴, 蔡光伟¹^,²^,⁴^,^†(

)

¹香港中文大学医学院妇产科学系产前遗传诊断中心，香港　999077
²香港中文大学卓越儿童健康研究所妇女儿童医学中心（深圳），深圳　518133
³南京大学医学院附属南京鼓楼医院妇产科产前诊断中心，南京　210008
⁴香港中文大学深圳研究院，深圳　518000
⁵吉林大学第一医院生殖医学·产前遗传中心，长春　130000

收稿日期:2026-03-22 修回日期:2026-07-20 出版日期:2026-08-01
通信作者: 蔡光伟

Application of genome sequencing in prenatal diagnosis

Yujie Zhu¹^,²^,³, Mengmeng Shi¹^,²^,⁴, Chunshu Jia⁵, Ye Cao¹^,²^,⁴, Kwong Wai Choy¹^,²^,⁴^,^†()

¹Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, Hong Kong Special Administrative Region, China;
²The Obstetric and Pediatric Center (Shenzhen) under Hong Kong Hub of Obstetric and Paediatric Excellence (HK HOPE), The Chinese University of Hong Kong, Shenzhen 518133, Guangdong Province, China;
³Prenatal Diagnosis Center, Center for Obstetrics and Gynecology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China;
⁴Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518000, Guangdong Province, China;
⁵Prenatal Diagnosis Center, Reproductive Medicine Center, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China

Received:2026-03-22 Revised:2026-07-20 Published:2026-08-01
Corresponding author: Kwong Wai Choy
Supported by:
National Key Research and Development Program of China(2023YFC2705603); Collaborative Research Fund by RGC of Hong Kong(C4062-21GF)

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朱雨捷, 史蒙蒙, 贾春澍, 曹也, 蔡光伟. 基因组测序技术在产前诊断中的应用[J/OL]. 中华妇幼临床医学杂志(电子版), 2026, 22(04): 283-289.

Yujie Zhu, Mengmeng Shi, Chunshu Jia, Ye Cao, Kwong Wai Choy. Application of genome sequencing in prenatal diagnosis[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2026, 22(04): 283-289.

中国历来高度重视出生缺陷的综合防治工作，产前诊断(prenatal diagnosis)作为三级防控体系的关键环节，对提升出生人口质量、落实优生优育政策具有重要的战略意义。随着染色体微阵列分析(CMA)和各类基于基因组测序(GS)技术的临床应用不断深入，产前诊断领域正经历深刻的技术变革。GS技术凭借其独特技术优势，不仅改变了产前诊断的临床实践模式，更推动着该领域迈入精准医学的全新发展阶段。然而，GS技术在产前诊断应用快速普及的同时，技术规范化应用的需求亦持续攀升。笔者拟系统梳理产前诊断技术的发展进程，重点分析GS技术在产前诊断中的适应证及其临床应用的循证数据与国际前沿的实践经验，并进一步展望GS多技术整合的发展趋势，旨在构建GS技术与产前诊断深度融合的优化协同策略，为中国产前诊断规范化和精准化提供理论依据与实践参考，同时为筑牢出生缺陷防控防线提供坚实的技术支撑。

关键词: 产前诊断, 微阵列分析, 全外显子测序, 全基因组测序, 长片段建库测序, 长读长测序技术

National policy of China has prioritized prevention and control of birth defects and congenital disabilities. Prenatal diagnosis, as a key component of the three-tier prevention system, plays a critical and strategically important role in carrying out measures for healthy childbirth and child-rearing. With the clinical application of chromosomal microarray analysis (CMA) and genome sequencing (GS) technologies, the field of prenatal diagnosis is undergoing significant advancements. GS technology is now transforming clinical practice and advancing the field toward precision medicine. However, as GS technology becomes rapidly popularized in prenatal applications, the demand for standardizing its application continues to rise. The authors aim to systematically review the development of prenatal diagnostic technologies, with a focus on the indications for GS in prenatal diagnosis, evidence from its clinical applications, and leading international practices, and to further explore future trends in the integration of multiple GS technologies. The goal is to develop an optimized strategy for deeply integrating GS technologies into prenatal diagnosis, provide a theoretical basis and practical reference for improving the standardization and precision of prenatal diagnosis in China, and simultaneously offer robust technical support for strengthening the prevention and control of birth defects.

Key words: Prenatal diagnosis, Chromosomal microarray analysis, Whole exome sequencing, Whole genome sequencing, Mate-pair sequencing, Long-read sequencing

表1 目前产前遗传学诊断中各类技术的检测范围与报告时间比较

检测技术	检测范围						报告时间
检测技术	非整倍体/重复序列	CNV	SV	SNV/indel	ROH	假基因序列	报告时间
G显带核型分析	√/×	√(5~10 Mb)	√(5~10 Mb)	×	×	×	14 d
CMA	√/×	√(50~100 kb)	×	×	√(SNP array)	×	7~14 d
DNA长片段建库测序技术(4×)	√/×	√(50~100 kb)	√(10 kb，不包括罗氏易位)	×	√(5 Mb)	×	21 d
WES	√/×	√(检测有限)	×	√(编码区域：1 bp)	√	×	21~28 d
GS(30×~50×)	√/√	√(<500 bp)	√(<500 bp，不包括罗氏易位)	√(编码及非编码区域：1 bp)	√(1 Mb)	√(检测有限)	14~28 d
LRS	√/√	√(50 bp)	√(<500 bp，不包括罗氏易位)	√(编码及非编码区域：1 bp)	√	√	不确定^a

表1 目前产前遗传学诊断中各类技术的检测范围与报告时间比较

检测技术	检测范围						报告时间
检测技术	非整倍体/重复序列	CNV	SV	SNV/indel	ROH	假基因序列	报告时间
G显带核型分析	√/×	√(5~10 Mb)	√(5~10 Mb)	×	×	×	14 d
CMA	√/×	√(50~100 kb)	×	×	√(SNP array)	×	7~14 d
DNA长片段建库测序技术(4×)	√/×	√(50~100 kb)	√(10 kb，不包括罗氏易位)	×	√(5 Mb)	×	21 d
WES	√/×	√(检测有限)	×	√(编码区域：1 bp)	√	×	21~28 d
GS(30×~50×)	√/√	√(<500 bp)	√(<500 bp，不包括罗氏易位)	√(编码及非编码区域：1 bp)	√(1 Mb)	√(检测有限)	14~28 d
LRS	√/√	√(50 bp)	√(<500 bp，不包括罗氏易位)	√(编码及非编码区域：1 bp)	√	√	不确定^a

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