Thompson Lauren, Larson Austin, Salz Lisa, Veith Regan, Tsai John-Paul, Jayakar Anuj, Chapman Rachel, Gupta Apeksha, Kingsmore Stephen F, Dimmock David, Bedrick Alan, Galindo Maureen Kelly, Casas Kari, Mohamed Mohamed, Straight Lisa, Khan M Akram, Salyakina Daria
Division of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, United States.
Department of Pediatrics, Children's Hospital Colorado, Aurora, CO, United States.
Front Pediatr. 2024 Feb 19;12:1349519. doi: 10.3389/fped.2024.1349519. eCollection 2024.
Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease.
rWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care.
A total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing.
Our study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.
在患有疑似遗传疾病的住院婴儿中多中心实施快速全基因组测序，并评估快速全基因组测序（rWGS）的临床效用，包括阳性、阴性和不确定结果。
2017年11月至2020年4月期间，在八家医院进行了rWGS检测。研究人员完成了一项关于人口统计学数据、人类表型本体论（HPO）术语、检测结果以及结果对临床护理影响的调查。
共有188名在综合医院病房和重症监护病房（ICU）的患者接受了rWGS检测。受试婴儿的种族和民族特征广泛代表了该国总体出生情况。35%的婴儿在中位时间6天内获得了诊断结果。受试婴儿最常见的HPO术语表明神经系统异常，其次是心血管系统、消化系统、呼吸系统以及头颈部。医疗服务提供者表示，总体上32%的受试婴儿以及70%获得诊断结果的婴儿因rWGS导致了临床管理的重大改变。此外，7%的rWGS结果为阴性的婴儿和23%的意义未明变异（VUS）婴儿因检测导致了管理上的重大改变。
我们的研究表明，rWGS在不同机构的实施是可行的，并提供了额外证据来支持rWGS在具有人口统计学代表性的住院婴儿样本中的临床效用，且除了阳性和阴性结果外，还包括对rWGS不确定结果的临床影响评估。
