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

被引：145

作者：

Ewans, Lisa J. ^{[1
,2
]}

Schofield, Deborah ^{[2
,3
,4
]}

Shrestha, Rupendra ^{[3
]}

Zhu, Ying ^{[5
,6
]}

Gayevskiy, Velimir ^{[2
]}

Ying, Kevin ^{[2
]}

Walsh, Corrina ^{[6
]}

Lee, Eric ^{[6
]}

Kirk, Edwin P. ^{[6
,7
,8
]}

Colley, Alison ^{[9
]}

Ellaway, Carolyn ^{[7
,10
,11
]}

Turner, Anne ^{[7
,8
]}

Mowat, David ^{[7
,8
]}

Worgan, Lisa ^{[9
]}

Freckmann, Mary-Louise ^{[7
,8
]}

Lipke, Michelle ^{[7
,12
]}

Sachdev, Rani ^{[7
,8
]}

Miller, David ^{[2
]}

Field, Michael ^{[5
]}

Dinger, Marcel E. ^{[1
,2
]}

Buckley, Michael F. ^{[6
]}

Cowley, Mark J. ^{[1
,2
]}

Roscioli, Tony ^{[6
,7
,13
,14
]}

机构：

[1] Univ New South Wales, St Vincents Clin Sch, Darlinghurst, NSW, Australia

[2] Garvan Inst Med Res, Kinghorn Ctr Clin Genom, Darlinghurst, NSW, Australia

[3] Univ Sydney, Charles Perkins Ctr, Fac Pharm, Sydney, NSW, Australia

[4] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic, Australia

[5] Genet Learning Disabil Serv, Waratah, NSW, Australia

[6] Prince Wales Hosp, Randwick Genet, NSW Hlth Pathol, Randwick, NSW, Australia

[7] Sydney Childrens Hosp, Clin Genet Ctr, Randwick, NSW, Australia

[8] Univ New South Wales, Sch Womens & Childrens Hlth, Sydney, NSW, Australia

[9] Liverpool Hosp, Dept Clin Genet, Liverpool, Merseyside, England

[10] Univ Sydney, Discipline Child & Adolescent Hlth, Sydney, NSW, Australia

[11] Univ Sydney, Discipline Genet Med, Sydney, NSW, Australia

[12] Lady Cilento Childrens Hosp, Brisbane, Qld, Australia

[13] Univ New South Wales, NeuRA, Kensington, NSW, Australia

[14] Univ New South Wales, Prince Wales Clin Sch, Kensington, NSW, Australia

来源：

GENETICS IN MEDICINE | 2018年 / 20卷 / 12期

基金：

英国医学研究理事会;

关键词：

cost-effectiveness; diagnosis; exome; genomics; Mendelian; METABOLIC CRISES; GENOME; MUTATIONS; TOOL;

D O I：

10.1038/gim.2018.39

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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%.

引用

页码：1564 / 1574

页数：11

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