Newborn screening (NBS) is performed to identify neonates at risk for actionable, severe, early-onset disorders, many of which are genetic. The BabySeq Project randomized neonates to receive conventional NBS or NBS plus exome sequencing (ES) capable of detecting sequence variants that may also diagnose monogenic disease or indicate genetic disease risk. We therefore evaluated how ES and conventional NBS results differ in this population.
We compared results of NBS (including hearing screens) and ES for 159 infants in the BabySeq Project. Infants were considered “NBS positive” if any abnormal result was found indicating disease risk and “ES positive” if ES identified a monogenic disease risk or a genetic diagnosis.
Most infants (132/159, 84%) were NBS and ES negative. Only one infant was positive for the same disorder by both modalities. Nine infants were NBS positive/ES negative, though seven of these were subsequently determined to be false positives. Fifteen infants were ES positive/NBS negative, all of which represented risk of genetic conditions that are not included in NBS programs. No genetic explanation was identified for eight infants referred on the hearing screen.
These differences highlight the complementarity of information that may be gleaned from NBS and ES in the newborn period.
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The genomic data/analyses reported in this paper have been deposited in the NBSTRN LPDR (https://nbstrn.org/tools/lpdr) under accession identifier nbs000002.v1.p1. Data access is restricted; for information on how to request access, please contact corresponding author Monica Wojcik at email@example.com or Pankaj Agrawal at firstname.lastname@example.org.
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M.H.W. is supported by K23 HD102589–01. Research reported in this publication was supported by the National Institutes of Health under award numbers R01HG009922, R01HL143295, U01TR003201, and U19HD077671. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The BCH’s Institutional Review Board (IRB) and the Partners Human Research Committee (the IRB for BWH) approved this study and informed consent was obtained from all participants as required by the IRB.
R.C.G. has received compensation for advising the following companies: AIA, Grail, Humanity, Kneed Media, Plumcare, UnitedHealth, Verily, VibrentHealth, Wamberg; and is co-founder of Genome Medical, Inc. P.B.A. is on the Clinical Advisory Board of Illumina Inc. and GeneDx. H.L.R. is a compensated scientific advisory board member of Genome Medical. The other authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Wojcik, M.H., Zhang, T., Ceyhan-Birsoy, O. et al. Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project. Genet Med (2021). https://doi.org/10.1038/s41436-021-01146-5