Open AccessDiagnostic and cost utility of whole exome sequencing in peripheral neuropathy
Author(s) -
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.
Publication year - 2017
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.409
Subject(s) - medicine , exome sequencing , peripheral neuropathy , cohort , exome , pediatrics , phenotype , gene , biochemistry , chemistry , diabetes mellitus , endocrinology
Abstract Objective To explore the diagnostic utility and cost effectiveness of whole exome sequencing ( WES ) in a cohort of individuals with peripheral neuropathy. Methods 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. Results 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. Conclusions 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.