Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Fifty patients with a peripheral neuropathy were recruited. 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.