Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR.
Key Laboratory for Regenerative Medicine, Ministry of Education (Shenzhen Base), Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen.
Curr Opin Obstet Gynecol. 2021 Apr 1;33(2):148-155. doi: 10.1097/GCO.0000000000000692.
Advancements in technologies have revolutionized prenatal diagnosis. Chromosomal microarray analysis (CMA) became a proven method and was implemented to detect gains and losses of DNA and absence of heterozygosity across the genome. Next-generation sequencing technologies have brought opportunities and challenges to genetic testing. Exome sequencing detects single-nucleotide variants (SNVs) across the exome and its prenatal application is an emerging field. We reviewed the literature to define the role of CMA and exome sequencing in prenatal diagnosis.
The application of exome sequencing in genetic diagnosis shows increased diagnostic yield and could be potentially implemented for prenatal diagnosis of fetuses with one or more ultrasound structural abnormalities or suspected monogenetic conditions. Although CMA is a gold standard for copy number variant (CNV) detection, large clinical cohort studies emphasized integrated CNV and SNV analyses for precise molecular diagnosis. Recent studies also suggest low-pass genome sequencing-based CNV detection can identify genome-wide imbalances at higher resolutions.
Data suggest exome sequencing for SNVs and CMA for CNV detection are the most effective approach for prenatal genetic diagnosis. Emerging evidences show genome sequencing has the potential to replace CMA and even exome sequencing to become a comprehensive genetic test in the clinical diagnostic laboratory.
技术的进步彻底改变了产前诊断。染色体微阵列分析 (CMA) 已成为一种经过验证的方法，并被用于检测整个基因组中 DNA 的增益和丢失以及杂合性缺失。新一代测序技术为基因检测带来了机遇和挑战。外显子组测序可检测外显子中单核苷酸变异 (SNV)，其在产前的应用是一个新兴领域。我们查阅了文献，以确定 CMA 和外显子组测序在产前诊断中的作用。
外显子组测序在遗传诊断中的应用显示出更高的诊断率，并且可能被潜在地用于对一个或多个超声结构异常或疑似单基因疾病的胎儿进行产前诊断。虽然 CMA 是检测拷贝数变异 (CNV) 的金标准，但大型临床队列研究强调了对 CNV 和 SNV 的综合分析，以进行精确的分子诊断。最近的研究还表明，基于低通全基因组测序的 CNV 检测可以以更高的分辨率识别全基因组的不平衡。
数据表明，用于 SNV 的外显子组测序和用于 CNV 检测的 CMA 是产前基因诊断最有效的方法。新出现的证据表明，基因组测序有可能取代 CMA，甚至外显子组测序，成为临床诊断实验室中的综合基因检测。
