SCI天天读|遗传诊断对既往难诊断疾病的作用

SCI

 6 December 2018

Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease

• Splinter K, Adams DR, Bacino CA, et al. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. The New England journal of medicine 2018;379:2131-9.

• Address reprint requests to Dr. Ashley at Stanford University, Falk Cardiovascular Research Bldg., 870 Quarry Rd., Stanford, CA 94304, or at [e-mail].

BACKGROUND 背景

Many 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.

尽管进行了全面的医疗检查，许多病人仍然没有得到最终诊断。建立未诊断疾病网络(UDN)，将多学科模式应用于最疑难病例的评估，和识别新发现疾病的生物学特征。UDN由美国国立卫生研究院(National Institutes of Health)资助，成立于2014年，是一个由七个临床站点、两个测序中心和一个协调中心组成的网络。随后，增加了一个生物库、代谢组学中心和一个模型生物筛选中心。

METHODS 方法

We 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.

我们评估了在20个月的时间内转诊到UDN的患者。这些患者必须是尽管经过了医务人员的全面检查评估，但疾病仍未确诊者。我们得出了经过完整评估的患者的诊断率，并观察了诊断对医疗活动的影响。

RESULTS 结果

A 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.

共有1519例患者(53%女性)被转诊到UDN，其中601例(40%)接受评估。在这些接受评估的患者中，192人(32%)曾接受过外显子组测序。症状为神经系统的占40%，肌肉骨骼的占10%，免疫系统的占7%，胃肠道的占7%，风湿病的占6%。在382例接受完整评估的患者中，132例得出了最终诊断，诊断率为35%。15例(11%)仅通过临床复习诊断，98例(74%)通过外显子组或基因组测序诊断。对于这些得出诊断的患者，21%的人被建议改变治疗方法，37%的人被建议改变检查方法，36%的人被建议改变基因咨询方法。我们定义了31种新的综合征。

CONCLUSIONS 结论

The UDN established a diagnosis in 132 of the 382 patients who had a complete evaluation, yielding a rate of diagnosis of 35%.

在382例完全评估的患者中，UDN确诊132例，诊断率35%。