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对疑似单基因疾病的危重患儿进行超快速基因组检测是可行的
作者:小柯机器人 发布时间:2020/6/24 14:49:08

澳大利亚基因组学健康联盟急救部分析了在澳大利亚公共卫生保健系统中对疑似单基因疾病的危重患儿进行超快速外显子组测序的可行性。该成果发表在2020年6月23日出版的《美国医学会杂志》上。

在儿科危重病监护中广泛采用快速基因组检测,需要强大的临床和实验室通道,以在整个医疗系统中提供公平一致的服务。

为了前瞻性地评估公共卫生保健系统中用于快速基因组诊断的多中心网络的性能,2018年3月至2019年2月,研究组对澳大利亚12家医院中收治的疑似单基因病重症患儿进行了一项描述性可行性研究,收集数据截至2019年5月。主要结果为从样品接收到超快速外显子组测序报告的时间。

研究队列共包括108名患儿,中位年龄为28天,女性占34%; 57%来自新生儿重症监护病房,33%来自儿科重症监护病房,9%来自其他医院病房。从样品接收到超快速外显子组测序报告的平均时间为3.3天,中位时间为3天。从入院到超快速外显子组测序报告的平均时间为17.5天,共有93篇报告(86%)在死亡或出院前发布。在55名患儿(51%)中建立了分子诊断。

11项诊断(20%)使用以下方法来增强标准外显子组测序分析,包括线粒体基因组测序分析、基于外显子组测序的拷贝数分析、使用国际数据库鉴定新的基因-疾病关联、以及其他表型和RNA分析。55例患儿中42例(76%)有分子诊断,53例患儿中6例(11%)无分子诊断,研究组认为超快速外显子组测序结果影响了临床治疗方案。12例患儿(11%)开始进行靶向治疗,14例患儿(13%)转向姑息治疗,19例患儿(18%)开始接受特定并发症的监测。

总之,在澳大利亚公共卫生保健系统中,对疑似单基因疾病的危重患儿进行超快速基因组检测是可行的。

附:英文原文

Title: Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System

Author: Sebastian Lunke, Stefanie Eggers, Meredith Wilson, Chirag Patel, Christopher P. Barnett, Jason Pinner, Sarah A. Sandaradura, Michael F. Buckley, Emma I. Krzesinski, Michelle G. de Silva, Gemma R. Brett, Kirsten Boggs, David Mowat, Edwin P. Kirk, Lesley C. Adès, Lauren S. Akesson, David J. Amor, Samantha Ayres, Anne Baxendale, Sarah Borrie, Alessandra Bray, Natasha J. Brown, Cheng Yee Chan, Belinda Chong, Corrina Cliffe, Martin B. Delatycki, Matthew Edwards, George Elakis, Michael C. Fahey, Andrew Fennell, Lindsay Fowles, Lyndon Gallacher, Megan Higgins, Katherine B. Howell, Lauren Hunt, Matthew F. Hunter, Kristi J. Jones, Sarah King, Smitha Kumble, Sarah Lang, Maelle Le Moing, Alan Ma, Dean Phelan, Michael C. J. Quinn, Anna Richards, Christopher M. Richmond, Jessica Riseley, Jonathan Rodgers, Rani Sachdev, Simon Sadedin, Luregn J. Schlapbach, Janine Smith, Amanda Springer, Natalie B. Tan, Tiong Y. Tan

Issue&Volume: 2020/06/23

Abstract: Importance  Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems.

Objective  To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system.

Design, Setting, and Participants  Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption.

Exposures  Ultra-rapid exome sequencing.

Main Outcomes and Measures  The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge.

Results  The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing–based copy number analysis, use of international databases to identify novel gene–disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%).

Conclusions and Relevance  This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

DOI: 10.1001/jama.2020.7671

Source: https://jamanetwork.com/journals/jama/article-abstract/2767327

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex