Monica H Wojcik1,2,3, Tian Zhang4, Ozge Ceyhan-Birsoy5, Casie A Genetti4, Matthew S Lebo6,7, Timothy W Yu4, Richard B Parad8, Ingrid A Holm4, Heidi L Rehm9,6,7, Alan H Beggs4, Robert C Green9,10,11, Pankaj B Agrawal12,13,14. 1. Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu. 2. Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu. 3. Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. monica.wojcik@childrens.harvard.edu. 4. Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. 5. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA. 7. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 8. Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 9. Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. 10. Department of Medicine (Genetics), Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 11. Ariadne Labs, Boston, MA, USA. 12. Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. pagrawal@enders.tch.harvard.edu. 13. Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. pagrawal@enders.tch.harvard.edu. 14. Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. pagrawal@enders.tch.harvard.edu.
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.
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.
Authors: Brittan Armstrong; Kurt D Christensen; Casie A Genetti; Richard B Parad; Jill Oliver Robinson; Carrie L Blout Zawatsky; Bethany Zettler; Alan H Beggs; Ingrid A Holm; Robert C Green; Amy L McGuire; Hadley Stevens Smith; Stacey Pereira Journal: Front Genet Date: 2022-04-27 Impact factor: 4.772
Authors: Nina B Gold; Steven M Harrison; Jared H Rowe; Jessica Gold; Elissa Furutani; Alessandra Biffi; Christine N Duncan; Akiko Shimamura; Leslie E Lehmann; Robert C Green Journal: HGG Adv Date: 2021-09-25
Authors: Abigail Veldman; Mensiena B G Kiewiet; Margaretha Rebecca Heiner-Fokkema; Marcel R Nelen; Richard J Sinke; Birgit Sikkema-Raddatz; Els Voorhoeve; Dineke Westra; Martijn E T Dollé; Peter C J I Schielen; Francjan J van Spronsen Journal: Int J Neonatal Screen Date: 2022-02-24