As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Besides, we can develop novel interventions directed at the molecular characteristics of genetic diseases in newborns. The implementation of genomics in NBS programs would provide an effective premise for the identification of the majority of genetic aberrations and primarily help in accurate guidance in treatment and better prediction. However, there are some debate correlated with the widespread application of genome sequencing in NBS due to some major concerns such as clinical analysis, result interpretation, storage of sequencing data, and communication of clinically relevant mutations to pediatricians and parents, along with the ethical, legal, and social implications (so-called ELSI). This review is focused on these critical issues and concerns about the expanding role of genomics in NBS for precision medicine. If WGS or WES is to be incorporated into NBS practice, considerations about these challenges should be carefully regarded and tackled properly to adapt the requirement of genome sequencing in the era of precision medicine.
Newborn screening Precision medicine Whole-genome sequencing Whole-exome sequencing Genomics
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This study was supported by the National Natural Science Foundation of China (NSFC) (grant nos. 31670851, 31470821, and 91530320) and National Key R&D Programs of China (2016YFC1306605).
Calonge N, et al. Committee report: method for evaluating conditions nominated for population-based screening of newborns and children. Genet Med. 2010;12(3):153–9.CrossRefPubMedGoogle Scholar
Loeber JG, et al. Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1. From blood spot to screening result. J Inherit Metab Dis. 2012;35(4):603–11.CrossRefPubMedGoogle Scholar
Moyer VA, et al. Expanding newborn screening: process, policy, and priorities. Hast Cent Rep. 2008;38(3):32–9.CrossRefGoogle Scholar
Ombrone D, et al. Expanded newborn screening by mass spectrometry: new tests, future perspectives. Mass Spectrom Rev, vol. 35; 2015. p. 71–84.Google Scholar
Wilson K, Kennedy SJ, Potter B, Geraghty MT, Chakraborty P. Developing a national newborn screening strategy for Canada. Health Law Rev. 2010;18:31–19.Google Scholar
Kapoor S, Gupta N, Kabra M. National newborn screening program still a hype or a hope now? Indian Pediatr. 2013;50(7):639–43.CrossRefPubMedGoogle Scholar
Grosse SD, et al. From public health emergency to public health service: the implications of evolving criteria for newborn screening panels. Pediatrics. 2006;117(3):923–9.CrossRefPubMedGoogle Scholar
Serving the family from birth to the medical home. Newborn screening: a blueprint for the future – a call for a national agenda on state newborn screening programs. Pediatrics. 2000;106(2 Pt 2):389–422.Google Scholar
Howard HC, et al. Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes. Eur J Hum Genet. 2015;23:1593–600.CrossRefPubMedPubMedCentralGoogle Scholar
Wade CH, Tarini BA, Wilfond BS. Growing up in the genomic era: implications of whole-genome sequencing for children, families, and pediatric practice. Annu Rev Genomics Hum Genet. 2013;14:535–55.CrossRefPubMedPubMedCentralGoogle Scholar
Castellani C, Massie J. Newborn screening and carrier screening for cystic fibrosis: alternative or complementary? Eur Respir J. 2014;43(1):20–3.CrossRefPubMedGoogle Scholar
Khoo SK, et al. Acquiring genome-wide gene expression profiles in Guthrie card blood spots using microarrays. Pathol Int. 2011;61(1):1–6.CrossRefPubMedGoogle Scholar
Hollegaard MV, et al. Archived neonatal dried blood spot samples can be used for accurate whole genome and exome-targeted next-generation sequencing. Mol Genet Metab. 2013;110(1–2):65–72.CrossRefPubMedGoogle Scholar
Burgard P, et al. Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2. From screening laboratory results to treatment, follow-up and quality assurance. J Inherit Metab Dis. 2012;35(4):613–25.CrossRefPubMedGoogle Scholar
de Ligt J, et al. Detection of clinically relevant copy number variants with whole-exome sequencing. Hum Mutat. 2013;34(10):1439–48.CrossRefPubMedGoogle Scholar