Noninvasive Prenatal Diagnosis of Single-Gene Diseases: The Next Frontier

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2020-01, Vol.66 (1), p.53-60
• Main Authors: Scotchman, Elizabeth, Chandler, Natalie J, Mellis, Rhiannon, Chitty, Lyn S
• Format: Article
• Language: English
• Subjects: Achondroplasia; Antigens; Cell-Free Nucleic Acids - genetics; Cell-Free Nucleic Acids - metabolism; Clinical medicine; Deoxyribonucleic acid; Diagnosis; Disease; Disorders; DNA; DNA methylation; Ethical standards; Families & family life; Female; Fetus - metabolism; Fetuses; Fibroblasts; Genes; Gestation; Growth factors; Haplotypes; Health care; Health care industry; Health services; Hemophilia; Humans; Innovations; Literature reviews; Medical diagnosis; Miscarriage; Mutation; Noninvasive Prenatal Testing - methods; Plasma; Pregnancy; Pregnant women; Prenatal diagnosis; Public health; Rh-Hr Blood-Group System - genetics; Social impact; Whole Exome Sequencing
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2019.304238

Cell-free fetal DNA (cffDNA) is present in the maternal blood from around 4 weeks gestation and makes up 5%-20% of the total circulating cell-free DNA (cfDNA) in maternal plasma. Presence of cffDNA has allowed development of noninvasive prenatal diagnosis (NIPD) for single-gene disorders. This can be performed from 9 weeks gestation and offers a definitive diagnosis without the miscarriage risk associated with invasive procedures. One of the major challenges is distinguishing fetal mutations in the high background of maternal cfDNA, and research is currently focusing on the technological advances required to solve this problem. Here, we review the literature to describe the current status of NIPD for monogenic disorders and discuss how the evolving methodologies and technologies are expected to impact this field in both the commercial and public healthcare setting. NIPD for single-gene diseases was first reported in 2000 and took 12 years to be approved for use in a public health service. Implementation has remained slow but is expected to increase as this testing becomes cheaper, faster, and more accurate. There are still many technical and analytical challenges ahead, and it is vital that discussions surrounding the ethical and social impact of NIPD take account of the considerations required to implement these services safely into the healthcare setting, while keeping up with the technological advances.