Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application?
Open accessAbstract
Diagnostic genome-wide sequencing (exome or genome sequencing and data analysis for high-penetrance disease-causing variants) in acutely ill infants appears to be clinically useful, but the value of this diagnostic test should be rigorously demonstrated before it is accepted as a standard of care. This white paper was developed by the Paediatric Task Team of the Global Alliance for Genomics and Health's Regulatory and Ethics Work Stream to address the question of how we can determine the clinical value of genome-wide sequencing in infants in an intensive care setting. After reviewing available clinical and ethics literature on this question, we conclude that evaluating diagnostic genome-wide sequencing as a comprehensive scan for major genetic disease (rather than as a large panel of single-gene tests) provides a practical approach to assessing its clinical value in acutely ill infants. Comparing the clinical value of diagnostic genome-wide sequencing to chromosomal microarray analysis, the current evidence-based standard of care, per case of serious genetic disease diagnosed provides a practical means of assessing clinical value. Scientifically rigorous studies of this kind are needed to determine if clinical genome-wide sequencing should be established as a standard of care supported by healthcare systems and insurers for diagnosis of genetic disease in seriously ill newborn infants.
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No agreement exists on how to assess rapid testing programs or what level of evidence should guide health care system funding.
“there is no consensus on how to evaluate rapid testing programs or what evidentiary threshold should be used for health care system funding.”
Genomic diagnosis is especially powerful for monogenic neurodevelopmental disorders and critically ill infants.
“The power of genomic diagnosis is especially clear for those presenting with monogenic neurodevelopmental disorders and critically ill infants135,136.”
From A brief history of human disease genetics (2020) · cites this paper as [135]
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- Authors
- Friedman, J. M., Bombard, Y., Cornel, M. C., Fernandez, C. V., Junker, A. K., Plon, S. E., Stark, Z., & Knoppers, B. M.
- Affiliations
- University of British Columbia (CA)
- St. Michael's Hospital (CA)
- Amsterdam Public Health (NL)
- Dalhousie University (CA)
- Baylor College of Medicine (US)
- The University of Melbourne (AU)
- McGill University (CA)
- Corresponding author
- Friedman, Jan M.
- ORCID
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 21
- Issue
- 2
- Pages
- 498-504
- ISSN
- 1098-3600 (ISSN-L)
- PMC
- PMC6752673
- OpenAlex
- W2808235019
- Cited by
- 44
- References
- 58
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 11 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 2
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Genome Canada
- Genome British Columbia
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Ethics and Legal Issues in Pediatric Healthcare
- Keywords
- whole genome sequencing, exome sequencing, infants, acute illness, intensive care, clinical value, diagnostic testing, chromosomal microarray analysis, standard of care, health insurance coverage, genomic medicine
- MeSH terms
- Whole Genome Sequencing, Acute Disease, Diagnostic Tests, Routine, Genetic Testing, Humans, Infant, Infant, Newborn, Infant, Newborn, Diseases, Intensive Care, Neonatal, Penetrance
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