Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease
Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease
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DOI：
10.1056/nejmoa1714458
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发表时间：
2018-11-29
影响因子：
158.5
通讯作者：
Ashley, E. A.
中科院分区：
文献类型：
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作者：
Splinter, K.;Adams, D. R.;Ashley, E. A.
尽管进行了广泛的医学评估，许多患者仍然没有诊断。未诊断疾病网络（UDN）的建立是为了应用多学科模型来评估最具挑战性的病例，并确定新发现疾病的生物学特征。UDN由美国国立卫生研究院资助，成立于2014年，是一个由七个临床中心、两个测序核心和一个协调中心组成的网络。后来，一个中央生物库，代谢组学的核心，和模式生物筛选center.METHODSWe评估的患者谁被称为UDN在一段时间内的20个月。尽管医疗保健提供者进行了彻底的评估，但患者仍被要求患有未确诊的疾病。我们确定了患者中的诊断率，随后进行了完整的评估，我们观察了诊断对医疗护理的影响。共有1519名患者（53%为女性）被转介到UDN，其中601人（40%）被接受评估。在接受的患者中，192例（32%）以前接受过外显子组测序。40%的申请人的症状是神经系统的，10%是肌肉骨骼的，7%是免疫系统的，7%是胃肠道的，6%是风湿性的。在382名接受完整评估的患者中，132名获得诊断，诊断率为35%。共有15例（11%）诊断是通过临床审查单独作出的，98例（74%）是通过外显子组或基因组测序作出的。在这些诊断中，21%导致了关于改变治疗的建议，37%导致了诊断测试的改变，36%导致了变异特异性遗传咨询。我们定义了31个新的syndromes.CONCLUSIONSSThe UDN建立了一个完整的评估，诊断率为35%的382例患者中的132个诊断。
BACKGROUNDMany patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central biorepository, a metabolomics core, and a model organisms screening center were added.METHODSWe evaluated patients who were referred to the UDN over a period of 20 months. The patients were required to have an undiagnosed condition despite thorough evaluation by a health care provider. We determined the rate of diagnosis among patients who subsequently had a complete evaluation, and we observed the effect of diagnosis on medical care.RESULTSA total of 1519 patients (53% female) were referred to the UDN, of whom 601 (40%) were accepted for evaluation. Of the accepted patients, 192 (32%) had previously undergone exome sequencing. Symptoms were neurologic in 40% of the applicants, musculoskeletal in 10%, immunologic in 7%, gastrointestinal in 7%, and rheumatologic in 6%. Of the 382 patients who had a complete evaluation, 132 received a diagnosis, yielding a rate of diagnosis of 35%. A total of 15 diagnoses (11%) were made by clinical review alone, and 98 (74%) were made by exome or genome sequencing. Of the diagnoses, 21% led to recommendations regarding changes in therapy, 37% led to changes in diagnostic testing, and 36% led to variant-specific genetic counseling. We defined 31 new syndromes.CONCLUSIONSThe UDN established a diagnosis in 132 of the 382 patients who had a complete evaluation, yielding a rate of diagnosis of 35%.