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Genome-wide sequencing in acutely ill infants: genomic medicine's critical application?
Jan M Friedman1, Yvonne Bombard2,3, Martina C Cornel4
1Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. jan.friedman@ubc.ca.
Insights
Diagnostic genome-wide sequencing shows promise for acutely ill infants. Rigorous studies comparing it to current standards are needed to establish its clinical value and potential as a standard of care.
Area of Science:
- Genomics
- Clinical Diagnostics
- Paediatric Medicine
Background:
- Diagnostic genome-wide sequencing (GWS) is increasingly used in critically ill infants.
- Its clinical utility requires rigorous demonstration before adoption as standard care.
- The Paediatric Task Team addressed GWS value in neonatal intensive care.
Purpose of the Study:
- To determine the clinical value of genome-wide sequencing in acutely ill infants.
- To propose a framework for evaluating GWS in this population.
- To compare GWS to existing diagnostic standards.
Main Methods:
- Literature review of clinical and ethics research.
- Conceptualizing GWS as a comprehensive genetic disease scan.
- Proposing comparative studies against chromosomal microarray analysis.
Main Results:
- Evaluating GWS as a comprehensive scan is a practical approach.
- Comparing GWS to chromosomal microarray analysis per diagnosed case offers a feasible assessment method.
- Current evidence necessitates further rigorous studies.
Conclusions:
- Diagnostic GWS is potentially clinically useful in acutely ill infants.
- Further research is essential to establish GWS as a standard of care.
- Healthcare systems and insurers need evidence to support GWS adoption.
Abstract:
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.