Alternatively, following a positive prenatal ultrasound scan for fetal abnormalities after 11 weeks of gestation, the option for invasive testing (e.g. chorionic villus sampling or amniocentesis) becomes available. In fetuses that exhibited multiple multisystem major structural and selected other abnormalities, NGS technology enabled the analysis of fetal genetic material obtained from the invasive procedure to allow for screening of multiple genes in one test (Mellis, Chandler and Chitty, 2018). Studies relating to the use of whole-genome sequencing (WGS) are still sparse, as whole-exome sequencing (WES), which captures only the ‘protein-encoding’ regions (exons) of the DNA, is still the method of choice (Lord et al., 2019). This offers broader possibilities to evaluate the fetus with structural anomalies, improving the delineation of the prognosis, yield and accuracy of diagnoses, providing better clinical utility and allowing better options for genetic counselling for parents (Kilby, 2021). In addition, it is also possible that the identification of prenatal pathological variants associated with structural anomalies might facilitate opportunities for antenatal therapies in some cases (e.g. mesenchymal stem cell transplantation).
Nina Fajs, Edinburgh Genetics
Kilby, M. D. (2021) ‘The role of next-generation sequencing in the investigation of ultrasound-identified fetal structural anomalies’, BJOG: An International Journal of Obstetrics and Gynaecology, 128(2), pp. 420–429. doi: 10.1111/1471-0528.16533.
Lord, J. et al. (2019) ‘Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study’, The Lancet, 393(10173), pp. 747–757. doi: 10.1016/S0140-6736(18)31940-8.
Mellis, R., Chandler, N. and Chitty, L. S. (2018) ‘Next-generation sequencing and the impact on prenatal diagnosis’, Expert Review of Molecular Diagnostics. Taylor & Francis, 18(8), pp. 689–699. doi: 10.1080/14737159.2018.1493924.