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

Autor: Ewans LJ; St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia. l.ewans@garvan.org.au.; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia. l.ewans@garvan.org.au., Schofield D; 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., Shrestha R; Faculty of Pharmacy, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia., Zhu Y; 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., Gayevskiy V; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Ying K; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Walsh C; Randwick Genetics, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia., Lee E; Randwick Genetics, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia., Kirk EP; 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., Colley A; Clinical Genetics Department, Liverpool Hospital, Liverpool, New South Wales, Australia., Ellaway C; Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.; Disciplines of Child and Adolescent Health and Genetic Medicine, University of Sydney, New South Wales, Australia., Turner A; 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., Mowat D; 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., Worgan L; Clinical Genetics Department, Liverpool Hospital, Liverpool, New South Wales, Australia., Freckmann ML; 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., Lipke M; Centre for Clinical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.; Lady Cilento Children's Hospital, Brisbane, Queensland, Australia., Sachdev R; 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., Miller D; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Field M; The Genetics of Learning Disability Service, Waratah, New South Wales, Australia., Dinger ME; 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., Buckley MF; Randwick Genetics, NSW Health Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia., Cowley MJ; 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., Roscioli T; 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.; NeuRA and Prince of Wales Clinical School, University of New South Wales, Kensington, Australia, New South Wales.
Jazyk: angličtina
Zdroj: Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2018 Dec; Vol. 20 (12), pp. 1564-1574. Date of Electronic Publication: 2018 Mar 29.
DOI: 10.1038/gim.2018.39
Abstrakt: 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%.
Databáze: MEDLINE
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