RT Journal Article
SR Electronic
T1 Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 721
OP 728
DO 10.1136/jmedgenet-2018-105396
VO 55
IS 11
A1 Lamia Mestek-Boukhibar
A1 Emma Clement
A1 Wendy D Jones
A1 Suzanne Drury
A1 Louise Ocaka
A1 Andrey Gagunashvili
A1 Polona Le Quesne Stabej
A1 Chiara Bacchelli
A1 Nital Jani
A1 Shamima Rahman
A1 Lucy Jenkins
A1 Jane A Hurst
A1 Maria Bitner-Glindzicz
A1 Mark Peters
A1 Philip L Beales
A1 Hywel J Williams
YR 2018
UL http://jmg.bmj.com/content/55/11/721.abstract
AB Background 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.Methods 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.Results 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).Conclusion 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.