The current and future impact of genome-wide sequencing on fetal precision medicine

• Published in: Human genetics Vol. 139; no. 9; pp. 1121 - 1130
• Main Authors: Sabbagh, Riwa, Van den Veyver, Ignatia B.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2020; Springer; Springer Nature B.V
• Subjects: Amniocentesis; Amniocentesis - methods; Aneuploidy; Biomedical and Life Sciences; Biomedicine; Chorionic Villi Sampling - methods; Copy number; Deoxyribonucleic acid; DNA; DNA microarrays; Female; Feto-Maternal Genomic Medicine; Fetus - cytology; Fetuses; Gene Function; Genes; Genetic Diseases, Inborn - diagnosis; Genetic Diseases, Inborn - genetics; Genetic disorders; Genetic screening; Genetic Testing - methods; Genome - genetics; Genomes; Genomics; High-Throughput Nucleotide Sequencing - methods; Human Genetics; Humans; Metabolic Diseases; Molecular Medicine; Next-generation sequencing; Precision medicine; Precision Medicine - methods; Pregnancy; Pregnant women; Prenatal care; Prenatal Care - methods; Resource utilization; Review; Villus; Whole Genome Sequencing
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-019-02088-4

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.