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Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders


PurposeWhole-exome sequencing (WES) has revolutionized Mendelian diagnostics, however, there is no consensus on the timing of data review in undiagnosed individuals and only preliminary data on the cost-effectiveness of this technology. We aimed to assess the utility of WES data reanalysis for diagnosis in Mendelian disorders and to analyze the cost-effectiveness of this technology compared with a traditional diagnostic pathway.MethodsWES was applied to a cohort of 54 patients from 37 families with a variety of Mendelian disorders to identify the genetic etiology. Reanalysis was performed after 12 months with an improved WES diagnostic pipeline. A comparison was made between costs of a modeled WES pathway and a traditional diagnostic pathway in a cohort with intellectual disability (ID).ResultsReanalysis of WES data at 12 months improved diagnostic success from 30 to 41% due to interim publication of disease genes, expanded phenotype data from referrer, and an improved bioinformatics pipeline. Cost analysis on the ID cohort showed average cost savings of US$586 (AU$782) for each additional diagnosis.ConclusionEarly application of WES in Mendelian disorders is cost-effective and reanalysis of an undiagnosed individual at a 12-month time point increases total diagnoses by 11%.GENETICS in MEDICINE advance online publication, 29 March 2018; doi:10.1038/gim.2018.39.

Type Journal
ISBN 1530-0366 (Electronic) 1098-3600 (Linking)
Authors Ewans, L. J.; Schofield, D.; Shrestha, R.; Zhu, Y.; Gayevskiy, V.; Ying, K.; Walsh, C.; Lee, E.; Kirk, E. P.; Colley, A.; Ellaway, C.; Turner, A.; Mowat, D.; Worgan, L.; Freckmann, M. L.; Lipke, M.; Sachdev, R.; Miller, D.; Field, M.; Dinger, M. E.; Buckley, M. F.; Cowley, M. J.; Roscioli, T.
Responsible Garvan Author (missing name)
Published Date 2018-03-29
Status Always Electronic
DOI 10.1038/gim.2018.39
URL link to publisher's version