Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children.
Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children.
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DOI：
10.1136/jmedgenet-2018-105396
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发表时间：
2018-11
影响因子：
4
通讯作者：
Williams HJ
中科院分区：
文献类型：
--
作者：
Mestek-Boukhibar L;Clement E;Jones WD;Drury S;Ocaka L;Gagunashvili A;Le Quesne Stabej P;Bacchelli C;Jani N;Rahman S;Jenkins L;Hurst JA;Bitner-Glindzicz M;Peters M;Beales PL;Williams HJ
罕见遗传病是入院儿科重症监护病房 (PICU) 的常见危险因素或直接原因。此类情况经常被怀疑，但在入院 PICU 时未被发现。明确的诊断信息极大地有助于富有同情心和有效的护理。因此，需要提供快速的基因诊断来为临床管理提供信息。迄今为止，全基因组测序（WGS）方法已被证明可以成功诊断部分患有罕见疾病的儿童，但结果可能需要几个月的时间才能报告。我们的目标是开发一个端到端的工作流程，以便在英国国家医疗服务 (NHS) 诊断环境中使用快速全基因组测序 (WGS) 来诊断危重儿童。我们寻求建立一个多学科快速儿科测序团队，用于病例选择、三重全基因组测序、快速生物信息学序列分析以及分阶段分析和报告系统，以优先考虑具有高因果关系的基因。对 24 名危重儿童进行三重全基因组测序，通过识别致病基因变异，对 10 名（42%）儿童进行了分子诊断。在这 10 人中，有 3 人 (30%) 的诊断结果对其临床管理产生了直接影响。在过去 14 次三人组中，达到临时诊断所需的最短时间为 4 天（中位时间 8.5 天）。快速全基因组测序可用于在 NHS 临床诊断环境的限制内诊断危重儿童并为其管理提供信息。我们提供强大的工作流程，为 NHS 和全球其他医疗保健系统中快速基因组测序的推广提供信息和便利。
Rare genetic conditions are frequent risk factors for, or direct causes of, paediatric intensive care unit (PICU) admission. Such conditions are frequently suspected but unidentified at PICU admission. Compassionate and effective care is greatly assisted by definitive diagnostic information. There is therefore a need to provide a rapid genetic diagnosis to inform clinical management. To date, whole genome sequencing (WGS) approaches have proved successful in diagnosing a proportion of children with rare diseases, but results may take months to report. Our aim was to develop an end-to-end workflow for the use of rapid WGS for diagnosis in critically ill children in a UK National Health Service (NHS) diagnostic setting. We sought to establish a multidisciplinary Rapid Paediatric Sequencing team for case selection, trio WGS, rapid bioinformatics sequence analysis and a phased analysis and reporting system to prioritise genes with a high likelihood of being causal. Trio WGS in 24 critically ill children led to a molecular diagnosis in 10 (42%) through the identification of causative genetic variants. In 3 of these 10 individuals (30%), the diagnostic result had an immediate impact on the individual’s clinical management. For the last 14 trios, the shortest time taken to reach a provisional diagnosis was 4 days (median 8.5 days). Rapid WGS can be used to diagnose and inform management of critically ill children within the constraints of an NHS clinical diagnostic setting. We provide a robust workflow that will inform and facilitate the rollout of rapid genome sequencing in the NHS and other healthcare systems globally.
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影响因子：
9.5
作者：
Thorvaldsdóttir H;Robinson JT;Mesirov JP
通讯作者：
Mesirov JP
影响因子：
4.6
作者：
Hwang S;Kim E;Lee I;Marcotte EM
通讯作者：
Marcotte EM
影响因子：
8
作者：
van Diemen, Cleo C.;Kerstjens-Frederikse, Wilhelmina S.;Wijmenga, Cisca
通讯作者：
Wijmenga, Cisca
影响因子：
3.4
作者：
Petrikin JE;Willig LK;Smith LD;Kingsmore SF
通讯作者：
Kingsmore SF
影响因子：
5.3
作者：
Meienberg J;Bruggmann R;Oexle K;Matyas G
通讯作者：
Matyas G