Division of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Primary Children's Center for Personalized Medicine, Salt Lake City, UT, USA.
Pediatr Res. 2022 Nov;92(5):1364-1369. doi: 10.1038/s41390-022-01965-5. Epub 2022 Feb 3.
Rapid next-generation sequencing (NGS) offers the potential to shorten the diagnostic process and improve the care of acutely ill children. The goal of this study was to report our findings, including benefits and limitations, of a targeted NGS panel and rapid genome sequencing (rGS) in neonatal and pediatric acute clinical care settings.
Retrospective analysis of patient characteristics, diagnostic yields, turnaround time, and changes in management for infants and children receiving either RapSeq, a targeted NGS panel for 4500+ genes, or rGS, at the University of Utah Hospital and Primary Children's Hospital, from 2015 to 2020.
Over a 5-year period, 142 probands underwent rapid NGS: 66 received RapSeq and 76 rGS. Overall diagnostic yield was 39%. In the majority of diagnostic cases, there were one or more changes in clinical care management. Of note, 7% of diagnoses identified by rGS would not have been identified by RapSeq.
Our results indicate that rapid NGS impacts acute pediatric care in real-life clinical settings. Although affected by patient selection criteria, diagnostic yields were similar to those from clinical trial settings. Future studies are needed to determine relative advantages, including cost, turnaround time, and benefits for patients, of each approach in specific clinical circumstances.
The use of comprehensive Mendelian gene panels and genome sequencing in the clinical setting allows for early diagnosis of patients in neonatal, pediatric, and cardiac intensive care units and impactful change in management. Diagnoses led to significant changes in management for several patients in lower acuity inpatient units supporting further exploration of the utility of rapid sequencing in these settings. This study reviews the limitations of comparing sequencing platforms in the clinical setting and the variables that should be considered in evaluating diagnostic rates across studies.
快速下一代测序（NGS）有可能缩短诊断过程并改善急性病儿童的护理。本研究的目的是报告我们在新生儿和儿科急性临床护理环境中使用靶向 NGS 面板和快速基因组测序（rGS）的发现，包括其益处和局限性。
对 2015 年至 2020 年在犹他大学医院和初级儿童医院接受 RapSeq（针对 4500 多个基因的靶向 NGS 面板）或 rGS 的婴儿和儿童的患者特征、诊断率、周转时间和管理变化进行回顾性分析。
在 5 年期间，142 名先证者接受了快速 NGS：66 名接受了 RapSeq，76 名接受了 rGS。总体诊断率为 39%。在大多数诊断病例中，临床管理发生了一次或多次变化。值得注意的是，rGS 确定的 7%的诊断结果无法通过 RapSeq 确定。
我们的结果表明，快速 NGS 会影响现实临床环境中的急性儿科护理。尽管受到患者选择标准的影响，但诊断率与临床试验环境中的诊断率相似。需要进一步的研究来确定每种方法在特定临床情况下的相对优势，包括成本、周转时间和对患者的益处。
综合孟德尔基因面板和基因组测序在临床环境中的使用可实现新生儿、儿科和心脏重症监护病房患者的早期诊断，并对管理产生重大影响。这些诊断导致了一些在低危住院病房的患者的管理发生了重大变化，这支持了在这些环境中进一步探索快速测序的实用性。本研究回顾了在临床环境中比较测序平台的局限性以及在评估不同研究中的诊断率时应考虑的变量。
