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基因诊断对疾病未确诊患者的影响
Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease


Kimberly Splinter ... 其他 • 2018.11.29

摘要


背景

许多患者虽然经过全面医学评估,但仍未得到诊断。建立未确诊疾病网络(undiagnosed diseases network,UDN)的目的是采用多学科模型评估最具挑战性的病例,并确定新发现疾病的生物学特征。由美国国立卫生研究院资助的UDN于2014年建立,是由7个临床研究中心、2个测序中心和1个协调中心组成的网络。随后又添加了1个中央生物样本库、1个代谢组学中心和1个模式生物筛选中心。

 

方法

我们评估了20个月期间被转诊至UDN的患者。研究要求患者虽然经医务人员的全面评估,但患未确诊的疾病。我们确定了随后接受全面评估的患者中的诊断率,并且观察了诊断对治疗的影响。

 

结果

总共1,519例患者(53%为女性)被转诊至UDN,其中601例(40%)被接收进行评估。在接收的患者中,192例(32%)既往接受过外显子组测序。40%的申请者有神经系统症状,10%有肌肉骨骼症状,7%有免疫系统症状,7%有胃肠道症状,6%有风湿病症状。在接受全面评估的382例患者中,132例得到诊断,诊断率为35%。共有15例诊断(11%)仅通过临床评估做出,98例(74%)通过外显子组或基因组测序得出。这些诊断导致的结果如下:21%建议改变治疗,37%改变诊断检查,36%接受变异体特异性遗传咨询。我们确定了31个新综合征。

 

结论

在接受全面评估的382例患者中,UDN得出了132例的诊断,诊断率为35%(由美国国立卫生研究院共同基金[National Institutes of Health Common Fund]资助)。





作者信息

Kimberly Splinter, M.S., David R. Adams, M.D., Ph.D., Carlos A. Bacino, M.D., Hugo J. Bellen, D.V.M., Ph.D., Jonathan A. Bernstein, M.D., Ph.D., Alys M. Cheatle-Jarvela, Ph.D., Christine M. Eng, M.D., Cecilia Esteves, M.P.H., William A. Gahl, M.D., Ph.D., Rizwan Hamid, M.D., Ph.D., Howard J. Jacob, Ph.D., Bijal Kikani, B.S., David M. Koeller, M.D., Isaac S. Kohane, M.D., Ph.D., Brendan H. Lee, M.D., Ph.D., Joseph Loscalzo, M.D., Ph.D., Xi Luo, Ph.D., Alexa T. McCray, Ph.D., Thomas O. Metz, Ph.D., John J. Mulvihill, M.D., Stanley F. Nelson, M.D., Christina G.S. Palmer, Ph.D., John A. Phillips, III, M.D., Leslie Pick, Ph.D., John H. Postlethwait, Ph.D., Chloe Reuter, M.S., Vandana Shashi, M.B., B.S., M.D., David A. Sweetser, M.D., Ph.D., Cynthia J. Tifft, M.D., Ph.D., Nicole M. Walley, M.S., Michael F. Wangler, M.D., Monte Westerfield, Ph.D., Matthew T. Wheeler, M.D., Ph.D., Anastasia L. Wise, Ph.D., Elizabeth A. Worthey, Ph.D., Shinya Yamamoto, D.V.M., Ph.D., and Euan A. Ashley, M.B., Ch.B., D.Phil. for the Undiagnosed Diseases Network*
From Harvard Medical School (K.S., C.E., I.S.K., J.L., A.T.M., D.A.S.), Brigham and Women’s Hospital (J.L.), and Massachusetts General Hospital (D.A.S.) — all in Boston; the National Institutes of Health Clinical Center (D.R.A., W.A.G., J.J.M., C.J.T.) and the National Human Genome Research Institute (A.L.W.), Bethesda, and the University of Maryland, College Park (A.M.C.-J., B.K., L.P.) — all in Maryland; Baylor College of Medicine, Houston (C.A.B., H.J.B., C.M.E., B.H.L., X.L., M.F.W., S.Y.); Stanford University, Stanford (J.A.B., C.R., M.T.W., E.A.A.), and the University of California, Los Angeles, Los Angeles (S.F.N., C.G.S.P.) — both in California; Vanderbilt University, Nashville (R.H., J.A.P.); HudsonAlpha Institute for Biotechnology, Huntsville, AL (H.J.J., E.A.W.); Oregon Health and Science University, Portland (D.M.K.); the Pacific Northwest National Laboratory, Richland, WA (T.O.M.); the University of Oregon, Eugene (J.H.P., M.W.); and Duke University, Durham, NC (V.S., N.M.W.). Address reprint requests to Dr. Ashley at Stanford University, Falk Cardiovascular Research Bldg., 870 Quarry Rd., Stanford, CA 94304, or at euan@stanford.edu. *A complete list of members of the Undiagnosed Diseases Network is provided in the Supplementary Appendix, available at NEJM.org.

 

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