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

Ewans, LJ; Schofield, D; Shrestha, R; Zhu, Y; Gayevskiy, V; Ying, K; Walsh, C; Lee, E; Kirk, EP; Colley, A; Ellaway, C; Turner, A; Mowat, D; Worgan, L; Freckmann, ML; Lipke, M; Sachdev, R; Miller, D; Field, M; Dinger, ME; Buckley, MF; Cowley, MJ; Roscioli, T

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

Ewans, LJ Schofield, D Shrestha, R Zhu, Y Gayevskiy, V Ying, K

Walsh, C Lee, E Kirk, EP Colley, A Ellaway, C Turner, A Mowat, D Worgan, L Freckmann, ML Lipke, M Sachdev, R Miller, D Field, M Dinger, ME Buckley, MF Cowley, MJ Roscioli, T

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Publication Type:: Journal Article
Citation:: Genetics in Medicine, 2018, 20 (12), pp. 1564 - 1574
Issue Date:: 2018-12-01

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Field	Value	Language
dc.contributor.author	Ewans, LJ	en_US
dc.contributor.author	Schofield, D	en_US
dc.contributor.author	Shrestha, R	en_US
dc.contributor.author	Zhu, Y	en_US
dc.contributor.author	Gayevskiy, V	en_US
dc.contributor.author	Ying, K https://orcid.org/0000-0001-6041-8773	en_US
dc.contributor.author	Walsh, C	en_US
dc.contributor.author	Lee, E	en_US
dc.contributor.author	Kirk, EP	en_US
dc.contributor.author	Colley, A	en_US
dc.contributor.author	Ellaway, C	en_US
dc.contributor.author	Turner, A	en_US
dc.contributor.author	Mowat, D	en_US
dc.contributor.author	Worgan, L	en_US
dc.contributor.author	Freckmann, ML	en_US
dc.contributor.author	Lipke, M	en_US
dc.contributor.author	Sachdev, R	en_US
dc.contributor.author	Miller, D	en_US
dc.contributor.author	Field, M	en_US
dc.contributor.author	Dinger, ME	en_US
dc.contributor.author	Buckley, MF	en_US
dc.contributor.author	Cowley, MJ	en_US
dc.contributor.author	Roscioli, T	en_US
dc.date.available	2018-01-31	en_US
dc.date.issued	2018-12-01	en_US
dc.identifier.citation	Genetics in Medicine, 2018, 20 (12), pp. 1564 - 1574	en_US
dc.identifier.issn	1098-3600	en_US
dc.identifier.uri	http://hdl.handle.net/10453/129444
dc.description.abstract	© 2018, American College of Medical Genetics and Genomics. Purpose: 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. Methods: 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). Results: 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. Conclusion: 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%.	en_US
dc.relation.ispartof	Genetics in Medicine	en_US
dc.relation.isbasedon	10.1038/gim.2018.39	en_US
dc.subject.classification	Genetics & Heredity	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Genetic Diseases, Inborn	en_US
dc.subject.mesh	Computational Biology	en_US
dc.subject.mesh	Phenotype	en_US
dc.subject.mesh	Cost-Benefit Analysis	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Genetic Testing	en_US
dc.subject.mesh	Intellectual Disability	en_US
dc.subject.mesh	Exome	en_US
dc.subject.mesh	Whole Exome Sequencing	en_US
dc.title	Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	20	en_US
utslib.for	0604 Genetics	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	20	en_US

Abstract:

© 2018, American College of Medical Genetics and Genomics. Purpose: 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. Methods: 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). Results: 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. Conclusion: 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%.

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http://hdl.handle.net/10453/129444