Whole exome and genome sequencing in mendelian disorders: a diagnostic and health economic analysis
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Published:2022-08-15
Issue:10
Volume:30
Page:1121-1131
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ISSN:1018-4813
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Container-title:European Journal of Human Genetics
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language:en
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Short-container-title:Eur J Hum Genet
Author:
Ewans Lisa J.ORCID, Minoche Andre E., Schofield DeborahORCID, Shrestha Rupendra, Puttick Clare, Zhu Ying, Drew AlexanderORCID, Gayevskiy Velimir, Elakis George, Walsh Corrina, Adès Lesley C., Colley Alison, Ellaway Carolyn, Evans Carey-Anne, Freckmann Mary-Louise, Goodwin Linda, Hackett Anna, Kamien Benjamin, Kirk Edwin P.ORCID, Lipke Michelle, Mowat David, Palmer ElizabethORCID, Rajagopalan SulekhaORCID, Ronan AnneORCID, Sachdev Rani, Stevenson William, Turner Anne, Wilson MeredithORCID, Worgan Lisa, Morel-Kopp Marie-Christine, Field MichaelORCID, Buckley Michael F., Cowley Mark J.ORCID, Dinger Marcel E.ORCID, Roscioli TonyORCID
Abstract
AbstractWhole genome sequencing (WGS) improves Mendelian disorder diagnosis over whole exome sequencing (WES); however, additional diagnostic yields and costs remain undefined. We investigated differences between diagnostic and cost outcomes of WGS and WES in a cohort with suspected Mendelian disorders. WGS was performed in 38 WES-negative families derived from a 64 family Mendelian cohort that previously underwent WES. For new WGS diagnoses, contemporary WES reanalysis determined whether variants were diagnosable by original WES or unique to WGS. Diagnostic rates were estimated for WES and WGS to simulate outcomes if both had been applied to the 64 families. Diagnostic costs were calculated for various genomic testing scenarios. WGS diagnosed 34% (13/38) of WES-negative families. However, contemporary WES reanalysis on average 2 years later would have diagnosed 18% (7/38 families) resulting in a WGS-specific diagnostic yield of 19% (6/31 remaining families). In WES-negative families, the incremental cost per additional diagnosis using WGS following WES reanalysis was AU$36,710 (£19,407;US$23,727) and WGS alone was AU$41,916 (£22,159;US$27,093) compared to WES-reanalysis. When we simulated the use of WGS alone as an initial genomic test, the incremental cost for each additional diagnosis was AU$29,708 (£15,705;US$19,201) whereas contemporary WES followed by WGS was AU$36,710 (£19,407;US$23,727) compared to contemporary WES. Our findings confirm that WGS is the optimal genomic test choice for maximal diagnosis in Mendelian disorders. However, accepting a small reduction in diagnostic yield, WES with subsequent reanalysis confers the lowest costs. Whether WES or WGS is utilised will depend on clinical scenario and local resourcing and availability.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
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