Walsh Maie, Bell Katrina M, Chong Belinda, Creed Emma, Brett Gemma R, Pope Kate, Thorne Natalie P, Sadedin Simon, Georgeson Peter, Phelan Dean G, Day Timothy, Taylor Jessica A, Sexton Adrienne, Lockhart Paul J, Kiers Lynette, Fahey Michael, Macciocca Ivan, Gaff Clara L, Oshlack Alicia, Yiu Eppie M, James Paul A, Stark Zornitza, Ryan Monique M
Murdoch Childrens Research Institute Melbourne Australia.
Royal Melbourne Hospital Melbourne Australia.
Ann Clin Transl Neurol. 2017 Apr 26;4(5):318-325. doi: 10.1002/acn3.409. eCollection 2017 May.
To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy.
Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected.
Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray.
This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes.
探讨全外显子组测序（WES）在一组周围神经病患者中的诊断效用和成本效益。
对2014年2月至2015年12月期间通过一家儿科和一家成人三级中心招募的个体进行单人WES检测。初始分析仅限于与周围神经病相关的55个基因的虚拟面板。结果无信息的患者对WES数据进行扩展分析。收集了每位患者为诊断目的进行的先前检查和评估的成本数据。
招募了50例周围神经病患者（中位年龄18岁；范围2 - 68岁）。从首次就诊到研究入组的中位时间为6年9个月（范围2个月 - 62年），每位患者先前为诊断目的进行的检查和评估的平均成本为4013澳元。11名个体通过虚拟面板获得诊断。8名个体在对WES数据进行扩展分析后获得诊断，使总体诊断率提高到38%。另外两名个体通过SNP微阵列被诊断出致病性拷贝数变异。
本研究提供了证据表明WES在周围神经病患者中具有高诊断效用且具有成本效益。对WES数据的扩展分析显著提高了在初始靶向分析中未找到诊断的患者的诊断率。这主要是由于新发现基因所致疾病的诊断以及复杂和非典型表型的解决。
