Córdoba Marta, Rodriguez-Quiroga Sergio Alejandro, Vega Patricia Analía, Salinas Valeria, Perez-Maturo Josefina, Amartino Hernán, Vásquez-Dusefante Cecilia, Medina Nancy, González-Morón Dolores, Kauffman Marcelo Andrés
Consultorio de Neurogenética, Centro Universitario de Neurologia y Division Neurologia, Hospital J.M.Ramos Mejia, Facultad de Medicina, UBA, Buenos Aires, Argentina.
Programa de Medicina de Precisión y Genómica Clínica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina.
PLoS One. 2018 Feb 1;13(2):e0191228. doi: 10.1371/journal.pone.0191228. eCollection 2018.
Diagnostic trajectories for neurogenetic disorders frequently require the use of considerable time and resources, exposing patients and families to so-called "diagnostic odysseys". Previous studies have provided strong evidence for increased diagnostic and clinical utility of whole-exome sequencing in medical genetics. However, specific reports assessing its utility in a setting such as ours- a neurogeneticist led academic group serving in a low-income country-are rare.
To assess the diagnostic yield of WES in patients suspected of having a neurogenetic condition and explore the cost-effectiveness of its implementation in a research group located in an Argentinean public hospital.
This is a prospective study of the clinical utility of WES in a series of 40 consecutive patients selected from a Neurogenetic Clinic of a tertiary Hospital in Argentina. We evaluated patients retrospectively for previous diagnostic trajectories. Diagnostic yield, clinical impact on management and economic diagnostic burden were evaluated.
We demonstrated the clinical utility of Whole Exome Sequencing in our patient cohort, obtaining a diagnostic yield of 40% (95% CI, 24.8%-55.2%) among a diverse group of neurological disorders. The average age at the time of WES was 23 (range 3-70). The mean time elapsed from symptom onset to WES was 11 years (range 3-42). The mean cost of the diagnostic workup prior to WES was USD 1646 (USD 1439 to 1853), which is 60% higher than WES cost in our center.
WES for neurogenetics proved to be an effective, cost- and time-saving approach for the molecular diagnosis of this heterogeneous and complex group of patients.
神经遗传性疾病的诊断过程通常需要耗费大量时间和资源，使患者及其家庭经历所谓的“诊断之旅”。先前的研究提供了有力证据，表明全外显子测序在医学遗传学中的诊断和临床效用有所提高。然而，在我们这样的环境中评估其效用的具体报告却很少，我们是一个由神经遗传学家领导的学术团队，服务于一个低收入国家。
评估全外显子测序（WES）对疑似患有神经遗传性疾病患者的诊断率，并探讨在阿根廷一家公立医院的研究团队中实施该技术的成本效益。
这是一项关于WES临床效用的前瞻性研究，研究对象为从阿根廷一家三级医院的神经遗传诊所连续选取的40例患者。我们回顾性评估了患者先前的诊断过程。评估了诊断率、对治疗管理的临床影响以及经济诊断负担。
我们证明了全外显子测序在我们的患者队列中的临床效用，在一组多样化的神经系统疾病中获得了40%（95%置信区间，24.8%-55.2%）的诊断率。进行WES时的平均年龄为23岁（范围3-70岁）。从症状出现到进行WES的平均时间为11年（范围3-42年）。WES之前诊断检查的平均成本为1646美元（1439美元至1853美元），比我们中心的WES成本高60%。
对于神经遗传学来说，WES被证明是一种有效、节省成本和时间的方法，可用于对这一异质性和复杂患者群体进行分子诊断。
