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Genet Med. 2018 Dec;20(12):1564-1574. doi: 10.1038/gim.2018.39. Epub 2018 Mar 29.

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

Author information

1
St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia. l.ewans@garvan.org.au.
2
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. l.ewans@garvan.org.au.
3
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
4
Faculty of Pharmacy, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
5
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
6
The Genetics of Learning Disability Service, Waratah, New South Wales, Australia.
7
Randwick Genetics, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia.
8
Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.
9
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
10
Clinical Genetics Department, Liverpool Hospital, Liverpool, New South Wales, Australia.
11
Disciplines of Child and Adolescent Health and Genetic Medicine, University of Sydney, New South Wales, Australia.
12
Lady Cilento Children's Hospital, Brisbane, Queensland, Australia.
13
St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.
14
NeuRA and Prince of Wales Clinical School, University of New South Wales, Kensington, Australia, New South Wales.

Abstract

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%.

KEYWORDS:

Mendelian; cost-effectiveness; diagnosis; exome; genomics

PMID:
29595814
DOI:
10.1038/gim.2018.39
[Indexed for MEDLINE]

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