@article{1c32238a2e7443dfa2e9b59d2338c55a,
title = "Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project",
abstract = "Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 (∼18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.",
keywords = "exome sequencing, hearing loss, inborn errors of metabolism, newborn screening, pathogenic",
author = "Roman, {Tamara S.} and Crowley, {Stephanie B.} and Roche, {Myra I.} and Foreman, {Ann Katherine M.} and O'Daniel, {Julianne M.} and Seifert, {Bryce A.} and Kristy Lee and Alicia Brandt and Chelsea Gustafson and DeCristo, {Daniela M.} and Strande, {Natasha T.} and Lori Ramkissoon and Milko, {Laura V.} and Phillips Owen and Sayanty Roy and Mai Xiong and Paquin, {Ryan S.} and Butterfield, {Rita M.} and Lewis, {Megan A.} and Souris, {Katherine J.} and Bailey, {Donald B.} and Christine Rini and Booker, {Jessica K.} and Powell, {Bradford C.} and Weck, {Karen E.} and Powell, {Cynthia M.} and Berg, {Jonathan S.}",
note = "Funding Information: D.B.B. is involved in an unrelated research study that receives contributed equipment and reagents from Asuragen and an unrelated research study that receives partial funding from Sarepta Therapeutics. B.C.P. is an investigator on a different research study that receives in-kind support (reagents and sequencing consumables) from Illumina (San Diego, CA). K.E.W. is President and Chair of the Executive Committee and Board of Directors for the Association for Molecular Pathology, a member of the Advisory Committee for the US FDA Medical Devices Molecular and Clinical Genetics Devices Panel, and a member of the Consultant Advisory Panel for BlueCross BlueShield of North Carolina. Funding Information: We thank the families who participated in the study. This work was funded by the National Human Genome Research Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health as part of the Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT) Program, U19 HD077632 . We gratefully acknowledge the UNC BioSpecimen Processing Facility and the UNC High-Throughput Sequencing Facility for their work in DNA extraction, sample preparation and exome sequencing, and Manyu Li and the UNC Hospitals Clinical Molecular Genetics Laboratory. We also thank Jason Reilly, Ian Wilhelmsen, Kirk Wilhelmsen, Dylan Young, and the Renaissance Computing Institute (RENCI) at UNC for bioinformatics analysis and expertise; Alexandra Arreola and Claire Edgerly for contributions to molecular analysis; and Lonna Mollison and Kathleen Wallace for their contributions to curating the NGS-NBS and additional findings gene lists. Funding Information: We thank the families who participated in the study. This work was funded by the National Human Genome Research Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health as part of the Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT) Program, U19 HD077632. We gratefully acknowledge the UNC BioSpecimen Processing Facility and the UNC High-Throughput Sequencing Facility for their work in DNA extraction, sample preparation and exome sequencing, and Manyu Li and the UNC Hospitals Clinical Molecular Genetics Laboratory. We also thank Jason Reilly, Ian Wilhelmsen, Kirk Wilhelmsen, Dylan Young, and the Renaissance Computing Institute (RENCI) at UNC for bioinformatics analysis and expertise; Alexandra Arreola and Claire Edgerly for contributions to molecular analysis; and Lonna Mollison and Kathleen Wallace for their contributions to curating the NGS-NBS and additional findings gene lists. Publisher Copyright: {\textcopyright} 2020 American Society of Human Genetics",
year = "2020",
month = oct,
day = "1",
doi = "10.1016/j.ajhg.2020.08.001",
language = "English (US)",
volume = "107",
pages = "596--611",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",
}
