Diagnostic yield of next-generation sequencing applied to neurological disorders
Diagnostic yield of next-generation sequencing applied to neurological disorders
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DOI：
10.1016/j.jocn.2019.06.041
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发表时间：
2019-09-01
影响因子：
2
通讯作者：
Leao, Miguel
中科院分区：
文献类型：
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作者：
Matos, Claudia Marques;Alonso, Isabel;Leao, Miguel
关于遗传病因学的知识呈指数增长，以及对以前无法治疗的疾病进行基因特异性治疗的趋势，要求神经科医生熟悉下一代测序 (NGS) 的优点和缺点。我们的目的是评估 NGS 研究在我们环境中临床实践中的诊断率。我们在一个葡萄牙中心对需要进行 NGS 研究的连续神经系统患者进行了一项为期 18 个月的回顾性横断面研究。总共 190 名患者（89 名儿童）的诊断率 (DR) 达到 33.2%。肌肉疾病的比例更高（DR 61.1%）。 20% 的患者获得了不确定的分子诊断。偶然发现 (IF) 率为 5.3%。我们发现临床外显子组的 DR 更好（52.6%。p < 0.05），尽管只有 14% 的患者使用这种方法进行了表征。肌肉疾病基因组的表现较好，但不具有统计显着性（DR 56.3% 对比总体 31.7%，p > 0.05）。几个表型组中患者数量的减少限制了对特定诊断率的解释。肌肉疾病基因组的更高产量表明，基因组可能是明确表型中更具成本效益的一线测试。对于异质表型和总体而言，基于 WES 的虚拟面板或临床外显子组应该受到青睐。我们每天提供的实践证据表明，由于我们卫生系统的限制，对于三分之一的病因不明的神经系统疾病患者，可以通过 NGS 得出明确的诊断。 (C) 2019 Elsevier Ltd. 保留所有权利。
The exponential knowledge on the genetic etiology and the trend towards genetically-specific therapies for previously untreatable disorders, requires neurologists to be familiar with the strengths and weaknesses of Next-Generation Sequencing (NGS). Our aim was to assess the diagnostic yield of NGS studies in clinical practice in our setting. We performed a retrospective, cross-sectional, 18 months long study, from a single Portuguese center, of consecutive neurological patients for whom a NGS study was requested. A diagnosis rate (DR) of 33.2% was achieved for a total of 190 patients (89 children). It was higher for muscle diseases (DR 61.1%). In 20%, an inconclusive molecular diagnosis was obtained. The rate of incidental findings (IF) was 5.3%. We found better DR for clinical exome (52.6%. p < 0.05) although only 14% of patients were characterized using this approach. The performance of gene panels for muscle diseases was better but not statistically significant (DR 56.3% vs. 31.7% overall, p > 0.05). The reduced number of patients in several phenotypic groups limits the interpretation of specific diagnostic yields. The better yield of gene panels for muscle diseases suggests that gene panels may be a more cost-effective first-line test in well-defined phenotypes. For heterogeneous phenotypes and overall, WES-based virtual panels or clinical exome should be favored. We present daily practice evidence that, with the constraints of our health system, for one third of the patients with neurological disorders of undetermined etiology a definitive diagnosis can be reached with NGS. (C) 2019 Elsevier Ltd. All rights reserved.