1. Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project.
- Author
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Roman TS, Crowley SB, Roche MI, Foreman AKM, O'Daniel JM, Seifert BA, Lee K, Brandt A, Gustafson C, DeCristo DM, Strande NT, Ramkissoon L, Milko LV, Owen P, Roy S, Xiong M, Paquin RS, Butterfield RM, Lewis MA, Souris KJ, Bailey DB Jr, Rini C, Booker JK, Powell BC, Weck KE, Powell CM, and Berg JS
- Subjects
- Breast Neoplasms genetics, Child, Preschool, Female, Genome, Human, Hearing Loss genetics, Heterozygote, Humans, Infant, Infant, Newborn, Male, Metabolic Diseases genetics, Neonatal Screening, North Carolina, Oculocerebrorenal Syndrome genetics, Ovarian Neoplasms genetics, Public Health methods, Exome Sequencing, Breast Neoplasms diagnosis, Genetic Testing statistics & numerical data, Hearing Loss diagnosis, Metabolic Diseases diagnosis, Oculocerebrorenal Syndrome diagnosis, Ovarian Neoplasms diagnosis
- 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., (Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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