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

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Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders.
Genetics in Medicine ( IF 8.8 ) Pub Date : 2018-Mar-29 , DOI: 10.1038/gim.2018.39
Lisa J Ewans _{1,

2} , Deborah Schofield _{2,

3,

4} , Rupendra Shrestha ₃ , Ying Zhu _{5,

6} , Velimir Gayevskiy ₂ , Kevin Ying ₂ , Corrina Walsh ₆ , Eric Lee ₆ , Edwin P Kirk _{6,

7,

8} , Alison Colley ₉ , Carolyn Ellaway _{7,

10} , Anne Turner _{7,

8} , David Mowat _{7,

8} , Lisa Worgan ₉ , Mary-Louise Freckmann _{7,

8} , Michelle Lipke _{7,

11} , Rani Sachdev _{7,

8} , David Miller ₂ , Michael Field ₅ , Marcel E Dinger _{1,

2} , Michael F Buckley ₆ , Mark J Cowley _{1,

2} , Tony Roscioli _{6,

7,

12}

Affiliation

St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.
Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
Faculty of Pharmacy, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
The Genetics of Learning Disability Service, Waratah, New South Wales, Australia.
Randwick Genetics, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
Clinical Genetics Department, Liverpool Hospital, Liverpool, New South Wales, Australia.
Disciplines of Child and Adolescent Health and Genetic Medicine, University of Sydney, New South Wales, Australia.
Lady Cilento Children's Hospital, Brisbane, Queensland, Australia.
NeuRA and Prince of Wales Clinical School, University of New South Wales, Kensington, Australia, New South Wales.

PurposeWhole-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.MethodsWES 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).ResultsReanalysis 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.ConclusionEarly 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%.GENETICS in MEDICINE advance online publication, 29 March 2018; doi:10.1038/gim.2018.39.

中文翻译：

12 个月时的全外显子组测序再分析可促进诊断，并且在早期应用于孟德尔疾病时具有成本效益。

目的全外显子组测序 (WES) 彻底改变了孟德尔诊断，但是，对于未确诊个体的数据审查时间并没有达成共识，只有关于该技术成本效益的初步数据。我们旨在评估 WES 数据再分析在孟德尔疾病诊断中的效用，并分析该技术与传统诊断途径相比的成本效益。方法 WES 应用于来自 37 个家庭的 54 名患有各种孟德尔疾病的患者的队列以确定遗传病因。12 个月后使用改进的 WES 诊断流程进行再分析。在智障 (ID) 队列中，对模型 WES 路径和传统诊断路径的成本进行了比较。结果由于疾病基因的临时发表、来自推荐人的表型数据的扩展以及生物信息学管道的改进，在 12 个月时重新分析 WES 数据将诊断成功率从 30% 提高到 41%。ID 队列的成本分析显示，每增加一次诊断，平均可节省 586 美元（782 澳元）的成本。结论在孟德尔疾病中早期应用 WES 具有成本效益，并且在 12 个月的时间点对未确诊的个体进行再分析会使总诊断率增加11%. GENETICS in MEDICINE 提前在线出版，2018 年 3 月 29 日；doi:10.1038/gim.2018.39。结论 WES 在孟德尔疾病中的早期应用具有成本效益，并且在 12 个月的时间点对未确诊个体进行再分析可使总诊断率提高 11%。《医学遗传学》高级在线出版物，2018 年 3 月 29 日；doi:10.1038/gim.2018.39。结论 WES 在孟德尔疾病中的早期应用具有成本效益，并且在 12 个月的时间点对未确诊个体进行再分析可使总诊断率提高 11%。《医学遗传学》高级在线出版物，2018 年 3 月 29 日；doi:10.1038/gim.2018.39。

更新日期：2018-03-30

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