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Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness

Genetics in Medicine (2018) | Download Citation




To systematically investigate the longer-term clinical and health economic impacts of genomic sequencing for rare-disease diagnoses.


We collected information on continuing diagnostic investigation, changes in management, cascade testing, and parental reproductive outcomes in 80 infants who underwent singleton whole-exome sequencing (WES).


The median duration of follow-up following result disclosure was 473 days. Changes in clinical management due to diagnostic WES results led to a cost saving of AU$1,578 per quality-adjusted life year gained, without increased hospital service use. Uninformative WES results contributed to the diagnosis of non-Mendelian conditions in seven infants. Further usual diagnostic investigations in those with ongoing suspicion of a genetic condition yielded no new diagnoses, while WES data reanalysis yielded four. Reanalysis at 18 months was more cost-effective than every 6 months. The parents of diagnosed children had eight more ongoing pregnancies than those without a diagnosis. Taking the costs and benefits of cascade testing and reproductive service use into account, there was an additional cost of AU$8,118 per quality-adjusted life year gained due to genomic sequencing.


These data strengthen the case for the early use of genomic testing in the diagnostic trajectory, and can guide laboratory policy on periodic WES data reanalysis.

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We thank all collaborators in the Melbourne Genomics Health Alliance Demonstration Project, and K. Hood for administrative support with preparation of the manuscript.


The study was funded by the founding organizations of the Melbourne Genomics Health Alliance (Royal Melbourne Hospital, Royal Children’s Hospital, University of Melbourne, Walter and Eliza Hall Institute, Murdoch Children's Research Institute, Australian Genome Research Facility, and CSIRO) and the State Government of Victoria (Department of Health and Human Services). The involvement of AGRF was supported by sponsorship from Bioplatforms Australia and the NCRIS program.

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Author notes

    • Khurshid Alam PhD

    Present address: School of Population and Global Health, The University of Western Australia, Perth, Australia


  1. Murdoch Children’s Research Institute, Melbourne, Australia

    • Zornitza Stark BMBCh DM
    • , Deborah Schofield PhD
    • , Luke Rynehart BEcon
    • , Khurshid Alam PhD
    • , Sebastian Lunke PhD
    • , Tiong Y. Tan MBBS PhD
    •  & Susan M. White MBBS
  2. Melbourne Genomics Health Alliance, Melbourne, Australia

    • Zornitza Stark BMBCh DM
    • , Melissa Martyn PhD
    • , Tiong Y. Tan MBBS PhD
    •  & Clara L. Gaff PhD
  3. Department of Paediatrics, University of Melbourne, Melbourne, Australia

    • Zornitza Stark BMBCh DM
    • , Melissa Martyn PhD
    • , Khurshid Alam PhD
    • , Tiong Y. Tan MBBS PhD
    • , Clara L. Gaff PhD
    •  & Susan M. White MBBS
  4. Faculty of Pharmacy, University of Sydney, Sydney, Australia

    • Deborah Schofield PhD
    •  & Rupendra Shrestha PhD
  5. Garvan Institute of Medical Research, Sydney, Australia

    • Deborah Schofield PhD


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The authors declare no conflicts of interest.

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Correspondence to Clara L. Gaff PhD.

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