Department of Obstetrics and Gynecology, Baylor College of Medicine, 1250 Moursund Street, Room 1025.14, Houston, TX, 77030, USA.
Pavilion for Women, Texas Children's Hospital, Houston, TX, USA.
Hum Genet. 2020 Sep;139(9):1121-1130. doi: 10.1007/s00439-019-02088-4. Epub 2019 Nov 21.
Next-generation sequencing and other genomic technologies are transforming prenatal and reproductive screening and testing for fetal genetic disorders at an unprecedented pace. Original approaches of screening and testing for fetal genetic and genomic disorders were focused on a few more prevalent conditions that were easily diagnosable with pre-genomic era diagnostic tools. First, chromosomal microarray analysis and then next-generation sequencing brought technology capable of more detailed genomic evaluation to prenatal genetic screening and diagnosis. This has facilitated parallel introduction of a variety of new tests on maternal blood samples, including expanded carrier screening and cell-free DNA-based non-invasive screening for fetal aneuploidy, selected copy number variants, and single-gene disorders. Genomic tests on fetal DNA samples, obtained primarily through amniocentesis or chorionic villus sampling, include chromosomal microarray analysis and gene panel and exome sequencing. All these form the diagnostic pillar of the emerging field of fetal precision medicine, but their implementation is associated with ethical, counseling and healthcare resource utilization challenges. We discuss where in the reproductive and prenatal care continuum these exciting new technologies are integrated, along with associated challenges. We propose areas of priority for research to gain the data in support of their responsible implementation into clinical reproductive and prenatal care.
下一代测序和其他基因组技术以前所未有的速度改变了产前和生殖筛查以及胎儿遗传疾病的检测。用于筛查和检测胎儿遗传和基因组疾病的原始方法主要集中在一些更常见的疾病上,这些疾病在基因组前时代的诊断工具下很容易诊断。首先,染色体微阵列分析,然后是下一代测序,为产前遗传筛查和诊断带来了更详细的基因组评估技术。这促进了各种新的基于母体血液样本的检测的平行引入,包括扩展的携带者筛查和基于无细胞 DNA 的非侵入性胎儿非整倍体、特定拷贝数变异和单基因疾病筛查。胎儿 DNA 样本的基因组检测主要通过羊膜穿刺术或绒毛膜活检获得,包括染色体微阵列分析以及基因面板和外显子组测序。所有这些都构成了胎儿精准医学这一新兴领域的诊断支柱,但它们的实施与伦理、咨询和医疗资源利用挑战有关。我们讨论了这些令人兴奋的新技术在生殖和产前护理连续体中的哪些部分得到了整合,以及相关的挑战。我们提出了优先研究领域,以获得数据支持它们在生殖和产前护理中的负责任实施。