@article{d2affbf05942428d8c2febd614d5db10,
title = "Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project",
abstract = "Purpose: 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. Methods: 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. Results: 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. Conclusion: These differences highlight the complementarity of information that may be gleaned from NBS and ES in the newborn period.",
author = "{BabySeq Project Team} and Wojcik, {Monica H.} and Tian Zhang and Ozge Ceyhan-Birsoy and Genetti, {Casie A.} and Lebo, {Matthew S.} and Yu, {Timothy W.} and Parad, {Richard B.} and Holm, {Ingrid A.} and Rehm, {Heidi L.} and Beggs, {Alan H.} and Green, {Robert C.} and Agrawal, {Pankaj B.} and Agrawal, {Pankaj B.} and Beggs, {Alan H.} and Betting, {Wendi N.} and Ozge Ceyhan-Birsoy and Christensen, {Kurt D.} and Dmitry Dukhovny and Shawn Fayer and Frankel, {Leslie A.} and Genetti, {Casie A.} and Chet Graham and Green, {Robert C.} and Guiterrez, {Amanda M.} and Maegan Harden and Holm, {Ingrid A.} and Krier, {Joel B.} and Lebo, {Matthew S.} and Levy, {Harvey L.} and Xingquan Lu and Kalotina Machini and McGuire, {Amy L.} and Murry, {Jaclyn B.} and Medha Naik and Nguyen, {Tiffany T.} and Parad, {Richard B.} and Peoples, {Hayley A.} and Stacey Pereira and Devan Petersen and Uma Ramamurthy and Vivek Ramanathan and Rehm, {Heidi L.} and Amy Roberts and Robinson, {Jill O.} and Serguei Roumiantsev and Schwartz, {Talia S.} and Truong, {Tina K.} and VanNoy, {Grace E.} and Waisbren, {Susan E.} and Yu, {Timothy W.}",
note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.",
year = "2021",
month = jul,
doi = "10.1038/s41436-021-01146-5",
language = "English (US)",
volume = "23",
pages = "1372--1375",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "7",
}