標題: Critical Trio Exome Benefits In-Time Decision-Making for Pediatric Patients With Severe Illnesses*
作者: Wu, En-Ting
Hwu, Wuh-Liang
Chien, Yin-Hsiu
Hsu, Ching
Chen, Ting-Fu
Chen, Nai-Qi
Chou, Hung-Chieh
Tsao, Po-Nien
Fan, Pi-Chuan
Tsai, I-Jung
Lin, Shuan-Pei
Hsieh, Wu-Shiun
Chang, Tung-Ming
Chen, Chi-Nien
Lee, Chen-Hao
Chou, Yen-Yin
Chiu, Pao-Chin
Tsai, Wen-Hui
Hsiung, Hann-Chang
Lai, Feipei
Lee, Ni-Chung
生醫工程研究所
Institute of Biomedical Engineering
關鍵字: genetic;pediatric intensive care unit;whole exome sequence
公開日期: 1-Nov-2019
摘要: Objectives: Critical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness. Design: Observational analysis. Method: We employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period. Setting: A tertiary referral Children's Hospital in Taiwan. Patients: Critically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled. Interventions: None. Measurements and Main Results: Around 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 +/- 1.1 working days (range, 4.3-9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis. Conclusions: The current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources.
URI: http://dx.doi.org/10.1097/PCC.0000000000002068
http://hdl.handle.net/11536/153234
ISSN: 1529-7535
DOI: 10.1097/PCC.0000000000002068
期刊: PEDIATRIC CRITICAL CARE MEDICINE
Volume: 20
Issue: 11
起始頁: 1021
結束頁: 1026
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