The Impact of Rapid Exome Sequencing on Medical Management of Critically Ill Children.
The Impact of Rapid Exome Sequencing on Medical Management of Critically Ill Children.
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DOI：
10.1016/j.jpeds.2020.06.020
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Bennett JT
中科院分区：
文献类型：
--
作者：
Freed AS;Clowes Candadai SV;Sikes MC;Thies J;Byers HM;Dines JN;Ndugga-Kabuye MK;Smith MB;Fogus K;Mefford HC;Lam C;Adam MP;Sun A;McGuire JK;DiGeronimo R;Dipple KM;Deutsch GH;Billimoria ZC;Bennett JT
评价快速外显子组测序（rES）在单个机构使用标准化流程对可能患有遗传性疾病的危重儿童的临床效用。提供证据证明rES应成为该患者人群的标准治疗。我们实施了一个流程，在一个机构为符合条件的儿童提供临床级的rES。资格包括：a）咨询遗传学家推荐rES，B）怀疑单基因疾病，c）预测影响住院管理的快速诊断，d）适当提供者提供的试验前咨询，以及e）4名遗传学家委员会的一致批准。将Trio外显子组测序发送至参考实验室，该参考实验室在7-10天内提供口头报告。前瞻性收集与rES相关的临床结局。从遗传学家，遗传咨询师，病理学家，儿科医生和重症监护儿科医生的输入收集，以确定与rES相关的管理变化。54例患者有资格在34个月的研究期间的rES。其中46人接受了rES，其中24人（52%）至少有一个与rES相关的管理变化。在20名（43%）患者中，实现了分子诊断，表明非诊断性外显子组在某些情况下可能会改变医疗管理。84%在rES要求下不到1个月，平均周转时间为9天。rES检测对疑似单基因疾病的危重患儿的管理具有重大影响，应被视为可提供协调遗传学专业知识的三级机构的标准护理。
To evaluate the clinical utility of rapid exome sequencing (rES) in critically ill children with likely genetic disease using a standardized process at a single institution. To provide evidence that rES with should become standard of care for this patient population. We implemented a process to provide clinical-grade rES to eligible children at a single institution. Eligibility included: a) recommendation of rES by a consulting geneticist, b) monogenic disorder suspected, c) rapid diagnosis predicted to affect inpatient management, d) pre-test counseling provided by an appropriate provider, and e) unanimous approval by a committee of 4 geneticists. Trio exome sequencing was sent to a reference laboratory that provided verbal report within 7–10 days. Clinical outcomes related to rES were prospectively collected. Input from geneticists, genetic counselors, pathologists, neonatologists and critical care pediatricians was collected to identify changes in management related to rES. 54 patients were eligible for rES over a 34 month study period. 46 of these underwent rES, 24 of which (52%) had at least one change in management related to rES. In 20 (43%) patients a molecular diagnosis was achieved, demonstrating that non-diagnostic exomes could change medical management in some cases. 84% were under 1 month old at rES request and mean turnaround time was 9 days. rES testing has a significant impact on the management of critically ill children with suspected monogenic disease and should be considered standard of care for tertiary institutions who can provide coordinated genetics expertise.
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影响因子：
5.3
作者：
Petrikin, Josh E.;Cakici, Julie A.;Kingsmore, Stephen F.
通讯作者：
Kingsmore, Stephen F.
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：
Clark, Michelle M.;Starke, Zornitza;Kingsmore, Stephen F.
通讯作者：
Kingsmore, Stephen F.
影响因子：
4
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
通讯作者：
Williams HJ