Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project.
Breast Neoplasms
/ diagnosis
Child, Preschool
Female
Genetic Testing
/ statistics & numerical data
Genome, Human
Hearing Loss
/ diagnosis
Heterozygote
Humans
Infant
Infant, Newborn
Male
Metabolic Diseases
/ diagnosis
Neonatal Screening
North Carolina
Oculocerebrorenal Syndrome
/ diagnosis
Ovarian Neoplasms
/ diagnosis
Public Health
/ methods
Exome Sequencing
exome sequencing
hearing loss
inborn errors of metabolism
newborn screening
pathogenic
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
27
02
2020
accepted:
24
07
2020
pubmed:
28
8
2020
medline:
1
12
2020
entrez:
28
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32853555
pii: S0002-9297(20)30269-X
doi: 10.1016/j.ajhg.2020.08.001
pmc: PMC7536575
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
596-611Subventions
Organisme : NICHD NIH HHS
ID : U19 HD077632
Pays : United States
Informations de copyright
Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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