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

Whole-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...

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Published in:	Genetics in medicine 2018-12, Vol.20 (12), p.1564-1574
Main Authors:	Ewans, Lisa J., Schofield, Deborah, Shrestha, Rupendra, Zhu, Ying, Gayevskiy, Velimir, Ying, Kevin, Walsh, Corrina, Lee, Eric, Kirk, Edwin P, Colley, Alison, Ellaway, Carolyn, Turner, Anne, Mowat, David, Worgan, Lisa, Freckmann, Mary-Louise, Lipke, Michelle, Sachdev, Rani, Miller, David, Field, Michael, Dinger, Marcel E., Buckley, Michael F., Cowley, Mark J, Roscioli, Tony
Format:	Article
Language:	eng
Subjects:	Computational Biology Cost analysis Cost control Cost-Benefit Analysis - economics cost-effectiveness diagnosis exome Exome - genetics Female Genetic Diseases, Inborn - diagnosis Genetic Diseases, Inborn - economics Genetic Diseases, Inborn - genetics Genetic Testing - economics Genetic Testing - trends genomics Humans Intellectual Disability - diagnosis Intellectual Disability - genetics Intellectual Disability - pathology Male Mendelian Phenotype Whole Exome Sequencing - economics Whole Exome Sequencing - trends
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Summary:	Whole-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. WES 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). Reanalysis 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. Early 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%.
ISSN:	1098-3600 1530-0366