Jacobs Journal of Genetics

Clinical Whole Exome Sequencing in an Academic Pediatric Hospital: Analyses of the Diagnostic Odyssey

Published on: 2018-03-01


Background: Whole exome sequencing (WES) is a genetic test that sequences all protein-coding regions, exons, in a patient’s genome to identify disease causing mutations. Patients who present with complex phenotypes, may have had previous genetic testing and spent significant time searching for a diagnosis, known as a diagnostic odyssey and WES may help to end the search. WES can also detect secondary findings and/or genetic variants in disease associated genes with uncertain clinical significance. This study is a retrospective chart review designed to describe the diagnostic odyssey of patients who have had WES testing ordered through Cincinnati Children’s Hospital Medical Center (CCHMC)
Methods: Electronic medical records were abstracted for 75 pediatric patients (21 years or younger) during July 1, 2013 – September 30, 2014. The Results Group consists of 34 patients who received their WES results by September 30, 2014.
Results: Fifty four patients (72%) in the study population presented with symptoms in infancy and 32 patients (43%) had WES ordered at school age (5-13 years old). Age of onset of symptoms versus age that WES was ordered was significantly different (PConclusions: The majority of patients in this study presented with symptoms in infancy and had WES at school age, indicating a long diagnostic odyssey prior to receiving WES testing. This timeframe may, in part, be due to lack of availability of earlier WES testing. The information presented in this study supports the use of WES as a possible first line genetic test when diagnosis is unclear.


Whole exome sequencing; diagnostic odyssey; secondary findings; variants of uncertain significance; complex phenotype