The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases.
The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases.
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DOI：
10.1038/gim.0b013e318232a005
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发表时间：
2012-01
影响因子：
8.8
通讯作者：
Adams, David
中科院分区：
文献类型：
--
作者：
Gahl, William A.;Markello, Thomas C.;Toro, Camilo;Fajardo, Karin Fuentes;Sincan, Murat;Gill, Fred;Carlson-Donohoe, Hannah;Gropman, Andrea;Pierson, Tyler Mark;Golas, Gretchen;Wolfe, Lynne;Groden, Catherine;Godfrey, Rena;Nehrebecky, Michele;Wahl, Colleen;Landis, Dennis M. D.;Yang, Sandra;Madeo, Anne;Mullikin, James C.;Boerkoel, Cornelius F.;Tifft, Cynthia J.;Adams, David
本报告介绍了美国国立卫生研究院未诊断疾病计划（UDP），详细介绍了该计划的基因组技术的应用，以建立诊断，并详细介绍了该计划的成功率在其头两年。对每名接受的研究参与者进行了广泛的表型分析。参与者和选定的家庭成员（29名患者和78名未受影响的家庭成员）的一个子集进行了一组完整的基因组分析，包括高密度SNP阵列和全外显子组或基因组分析。在审查的1191份病历中，326名患者被接受，160名患者通过UDP服务直接进入NIH临床中心。其中，47%是儿童，55%是女性，53%患有神经系统疾病。39名参与者（24%）在临床，生化，病理或分子基础上获得诊断; 21例诊断涉及罕见或超罕见疾病。基于SNP阵列分析诊断了三种疾病，使用WES和变体过滤诊断了另外三种疾病。发现了两种新的疾病。SNP阵列研究队列的分析显示，相对于对照组，受影响的参与者中大范围的纯合性更常见。NIH UDP解决了一个未满足的需求，即，诊断患有复杂的多系统疾病的患者。它可以作为新兴基因组技术临床应用的模型，并提供深入了解在广泛的临床检查后仍未诊断的疾病的特征。
This report describes the NIH Undiagnosed Diseases Program (UDP), details the Program's application of genomic technology to establish diagnoses, and details the Program's success rate over its first two years. Each accepted study participant was extensively phenotyped. A subset of participants and selected family members (29 patients and 78 unaffected family members) was subjected to an integrated set of genomic analyses including high-density SNP arrays and whole exome or genome analysis. Of 1191 medical records reviewed, 326 patients were accepted and 160 were admitted directly to the NIH Clinical Center on the UDP service. Of those, 47% were children, 55% were females, and 53% had neurological disorders. Diagnoses were reached on 39 participants (24%) on clinical, biochemical, pathological, or molecular grounds; 21 diagnoses involved rare or ultra-rare diseases. Three disorders were diagnosed based upon SNP array analysis and three others using WES and filtering of variants. Two new disorders were discovered. Analysis of the SNP-array study cohort revealed that large stretches of homozygosity were more common in affected participants relative to controls. The NIH UDP addresses an unmet need, i.e., the diagnosis of patients with complex, multisystem disorders. It may serve as a model for the clinical application of emerging genomic technologies, and is providing insights into the characteristics of diseases that remain undiagnosed after extensive clinical workup.
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影响因子：
11
作者：
de Bot, S. T.;van den Elzen, R. T. M.;Scheffer, H.
通讯作者：
Scheffer, H.
影响因子：
3.5
作者：
Colgan, Sean P;Eltzschig, Holger K;Eckle, Tobias;Thompson, Linda F
通讯作者：
Thompson, Linda F
影响因子：
9.8
作者：
Allingham, RR;Seo, B;Vance, JM
通讯作者：
Vance, JM
影响因子：
3.9
作者：
Bonn, Florian;Pantakani, Krishna;Mannan, Ashraf U.
通讯作者：
Mannan, Ashraf U.
影响因子：
2
作者：
Manoli, Irini;Golas, Gretchen;Westbroek, Wendy;Vilboux, Thierry;Markello, Thomas C.;Introne, Wendy;Maynard, Dawn;Pederson, Ben;Tsilou, Ekaterini;Jordan, Michael B.;Hart, P. Suzanne;White, James G.;Gahl, William A.;Huizing, Marjan
通讯作者：
Huizing, Marjan