Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
Genet Med. 2019 Feb;21(2):498-504. doi: 10.1038/s41436-018-0055-z. Epub 2018 Jun 12.
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.
对急性病婴儿进行诊断性全基因组测序（外显子组或基因组测序和高外显率致病变异数据分析）似乎具有临床应用价值，但在将其作为常规护理标准接受之前，应严格证明该诊断测试的价值。本白皮书由全球基因组与健康联盟监管与伦理工作流儿科任务组制定，旨在解决如何确定重症监护环境中婴儿全基因组测序的临床价值这一问题。在对这一问题的现有临床和伦理文献进行审查后，我们得出结论，将诊断性全基因组测序作为主要遗传疾病的全面筛查（而不是作为一组大型单基因测试）进行评估，为评估其在急性病婴儿中的临床价值提供了一种实用方法。将诊断性全基因组测序的临床价值与当前基于证据的标准护理——染色体微阵列分析进行比较，每例确诊的严重遗传疾病都为评估临床价值提供了一种实用方法。需要进行此类严格的科学研究，以确定是否应将临床全基因组测序确立为支持医疗保健系统和保险公司的常规护理标准，用于诊断严重患病新生儿的遗传疾病。
