Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.
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DOI：
10.1126/scitranslmed.3010076
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发表时间：
2014-12-03
影响因子：
17.1
通讯作者：
Kingsmore SF
中科院分区：
文献类型：
--
作者：
Soden SE;Saunders CJ;Willig LK;Farrow EG;Smith LD;Petrikin JE;LePichon JB;Miller NA;Thiffault I;Dinwiddie DL;Twist G;Noll A;Heese BA;Zellmer L;Atherton AM;Abdelmoity AT;Safina N;Nyp SS;Zuccarelli B;Larson IA;Modrcin A;Herd S;Creed M;Ye Z;Yuan X;Brodsky RA;Kingsmore SF
神经发育障碍（NDD）影响超过3%的儿童，可归因于1000多个位点的单基因突变。传统方法在不到一半的NDD儿童中进行分子诊断。全基因组测序（WGS）和全外显子组测序（WES）可以诊断NDD，但其临床和成本效益尚不清楚。一百个家庭，119名儿童受NDD接受诊断性WGS和/或WES的父母-孩子三人组，其中测序方法是由疾病的急性指导。45%的人接受了分子诊断。一种加速的测序方式，快速WGS，在73%的急性病儿童家庭（11/15）中得到诊断。40%的非急性NDD儿童家庭，在门诊护理诊所（85人中的34人）接受诊断：33人通过WES和1人通过分期WES然后WGS。非急性患者既往阴性检测的成本为每个家庭19，100美元，这表明测序具有成本效益，每个家庭高达7640美元。49%的新诊断家庭报告了临床护理或病理生理学印象的变化。如果在症状发作时进行WES或WGS，则基因组诊断可能比本研究中发生的时间早77个月。建议NDD儿童的初始诊断评估应包括三重WGS或WES，并将加速测序模式扩展到高敏度患者。
Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients.
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影响因子：
2.4
作者：
Bartnik, Magdalena;Nowakowska, Beata;Derwinska, Katarzyna;Wisniowiecka-Kowalnik, Barbara;Kedzior, Marta;Bernaciak, Joanna;Ziemkiewicz, Kamila;Gambin, Tomasz;Sykulski, Maciej;Bezniakow, Natalia;Korniszewski, Lech;Kutkowska-Kazmierczak, Anna;Klapecki, Jakub;Szczaluba, Krzysztof;Shaw, Chad A.;Mazurczak, Tadeusz;Gambin, Anna;Obersztyn, Ewa;Bocian, Ewa;Stankiewicz, Pawel
通讯作者：
Stankiewicz, Pawel
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.4
作者：
Dinwiddie DL;Smith LD;Miller NA;Atherton AM;Farrow EG;Strenk ME;Soden SE;Saunders CJ;Kingsmore SF
通讯作者：
Kingsmore SF
影响因子：
3.9
作者：
Belet, Stefanie;Fieremans, Nathalie;Froyen, Guy
通讯作者：
Froyen, Guy