Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science.
Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science.
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DOI：
10.1038/s41436-020-00984-z
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Shashi V
中科院分区：
文献类型：
--
作者：
Schoch K;Esteves C;Bican A;Spillmann R;Cope H;McConkie-Rosell A;Walley N;Fernandez L;Kohler JN;Bonner D;Reuter C;Stong N;Mulvihill JJ;Novacic D;Wolfe L;Abdelbaki A;Toro C;Tifft C;Malicdan M;Gahl W;Liu P;Newman J;Goldstein DB;Hom J;Sampson J;Wheeler MT;Undiagnosed Diseases Network;Cogan J;Bernstein JA;Adams DR;McCray AT;Shashi V
NIH未诊断疾病网络（UDN）评估患有无法诊断的疾病的参与者，应用个性化的临床和基因组评估以及创新研究。UDN的临床研究中心对于推进UDN的使命至关重要;本研究评估了它们相对于标准临床实践的贡献。我们分析了2015年7月至2019年9月期间四个UDN临床研究中心的回顾性数据，以了解诊断、新疾病基因发现和基础研究方法。在791名接受评估的个体中，231人接受了240项诊断，并确认了17个新的疾病基因关联。UDN外显子组和基因组测序的直接诊断发生在35%（84/240）。我们认为这些在标准临床实践中是容易处理的，尽管基因组测序在临床上还没有广泛应用。大多数（156/240，65%）需要额外的UDN驱动的调查，包括90个诊断发生在先前的非诊断外显子组测序和45个诊断（19%）是非遗传性的。UDN驱动的研究包括互补/补充表型分析、基因组变异的创新分析以及功能测定和动物建模的协作科学。由临床研究中心推动的调查确定了超越标准诊断过程的诊断和研究范式。新的诊断，疾病基因的发现和新疾病的描述代表了基因组医学和科学的模式。
The NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices. We analyzed retrospective data from four UDN clinical sites, from July 2015-September 2019, for diagnoses, new disease gene discoveries and the underlying investigative methods. Of 791 evaluated individuals, 231 received 240 diagnoses and 17 new disease-gene associations were recognized. Straightforward diagnoses on UDN exome and genome sequencing occurred in 35% (84/240). We considered these tractable in standard clinical practice, although genome sequencing is not yet widely available clinically. The majority (156/240, 65%) required additional UDN-driven investigations, including 90 diagnoses that occurred after prior non-diagnostic exome sequencing and 45 diagnoses (19%) that were non-genetic. The UDN-driven investigations included complementary/supplementary phenotyping, innovative analyses of genomic variants and collaborative science for functional assays and animal modeling. Investigations driven by the clinical sites identified diagnostic and research paradigms that surpass standard diagnostic processes. The new diagnoses, disease gene discoveries and delineation of novel disorders represent a model for genomic medicine and science.
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影响因子：
14.9
作者：
Köhler S;Doelken SC;Mungall CJ;Bauer S;Firth HV;Bailleul-Forestier I;Black GC;Brown DL;Brudno M;Campbell J;FitzPatrick DR;Eppig JT;Jackson AP;Freson K;Girdea M;Helbig I;Hurst JA;Jähn J;Jackson LG;Kelly AM;Ledbetter DH;Mansour S;Martin CL;Moss C;Mumford A;Ouwehand WH;Park SM;Riggs ER;Scott RH;Sisodiya S;Van Vooren S;Wapner RJ;Wilkie AO;Wright CF;Vulto-van Silfhout AT;de Leeuw N;de Vries BB;Washingthon NL;Smith CL;Westerfield M;Schofield P;Ruef BJ;Gkoutos GV;Haendel M;Smedley D;Lewis SE;Robinson PN
通讯作者：
Robinson PN
影响因子：
158.5
作者：
Splinter, K.;Adams, D. R.;Ashley, E. A.
通讯作者：
Ashley, E. A.
影响因子：
8.8
作者：
Fennell, Andrew Paul;Hunter, Matthew Frank;Corboy, Gregory Philip
通讯作者：
Corboy, Gregory Philip
影响因子：
8.8
作者：
Schoch, Kelly;Tan, Queenie K. -G.;Shashi, Vandana
通讯作者：
Shashi, Vandana
基因组数据的系统重新分析可提高变异解释的质量。
影响因子：
3.5
作者：
Hiatt SM;Amaral MD;Bowling KM;Finnila CR;Thompson ML;Gray DE;Lawlor JMJ;Cochran JN;Bebin EM;Brothers KB;East KM;Kelley WV;Lamb NE;Levy SE;Lose EJ;Neu MB;Rich CA;Simmons S;Myers RM;Barsh GS;Cooper GM
通讯作者：
Cooper GM