Farnaes Lauge, Hildreth Amber, Sweeney Nathaly M, Clark Michelle M, Chowdhury Shimul, Nahas Shareef, Cakici Julie A, Benson Wendy, Kaplan Robert H, Kronick Richard, Bainbridge Matthew N, Friedman Jennifer, Gold Jeffrey J, Ding Yan, Veeraraghavan Narayanan, Dimmock David, Kingsmore Stephen F
Rady Children's Institute for Genomic Medicine, San Diego, CA USA.
2Department of Pediatrics, University of California San Diego, San Diego, CA USA.
NPJ Genom Med. 2018 Apr 4;3:10. doi: 10.1038/s41525-018-0049-4. eCollection 2018.
Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands also received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests ( = .0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; = .0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000-$2,000,000. These findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.
遗传性疾病是婴儿发病和死亡的主要原因。快速全基因组测序（rWGS）能够及时诊断遗传性疾病，从而改变急性医疗或外科治疗方案（临床效用），并改善急病婴儿的治疗效果。我们报告了一项针对2016年7月至2017年3月期间一家地区儿童医院急病住院婴儿的回顾性队列研究。42个家庭接受了rWGS以进行遗传性疾病的病因诊断。先证者也根据临床指征接受了标准基因检测。主要终点为诊断率、临床效用和医疗资源利用情况。通过比较实际利用情况与匹配的历史对照，以及/或者如果在不同时间点进行rWGS时的反事实利用情况，对6名婴儿的医疗资源利用情况进行了建模。rWGS的诊断敏感性为43%（42名婴儿中的18名），标准基因检测的诊断敏感性为10%（42名婴儿中的4名）（P = 0.0005）。rWGS的临床效用率（31%，42名婴儿中的13名）显著高于标准基因检测（2%，42名婴儿中的1名；P = 0.0015）。11名（26%）通过rWGS确诊的婴儿避免了发病，1名婴儿死亡可能性降低了43%，1名婴儿开始接受姑息治疗。在这11名婴儿中的6名中，治疗方案的改变使住院费用降低了80万美元至200万美元。这些发现重复了之前一项关于rWGS在急病住院婴儿中的临床效用的研究，并证明了治疗效果的改善和医疗净节约。在这种情况下，rWGS值得作为一线检测方法加以考虑。
