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. 2017 Jun;6(2):61-76.
doi: 10.1055/s-0036-1593968. Epub 2016 Nov 28.

Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic

David Bick  1 , Pamela C Fraser  2 , Michael F Gutzeit  3 , Jeremy M Harris  4 , Tina M Hambuch  5 , Daniel C Helbling  6 , Howard J Jacob  1 , Juliet N Kersten  3 , Steven R Leuthner  7 , Thomas May  1   8 , Paula E North  7 , Sasha Z Prisco  9 , Bryce A Schuler  10 , Mary Shimoyama  11 , Kimberly A Strong  12 , Scott K Van Why  13 , Regan Veith  14 , James Verbsky  15 , Arthur M Weborg Jr  4 , Brandon M Wilk  4 , Rodney E Willoughby Jr  13 , Elizabeth A Worthey  4 , David P Dimmock  16
Affiliations

Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic

David Bick et al. J Pediatr Genet. 2017 Jun.

Abstract

A pilot program was initiated using whole genome sequencing (WGS) to diagnose suspected genetic disorders in the Genetics Clinic at Children's Hospital of Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we obtained a 14% (3/22) diagnosis rate over 2 years; with subsequent reanalysis, this increased to 36% (8/22). Disease causing variants were identified in SKIV2L, CECR1, DGKE, PYCR2, RYR1, PDGFRB, EFTUD2, and BCS1L. In 75% (6/8) of diagnosed cases, the diagnosis affected treatment and/or medical surveillance. Additionally, one case demonstrated a homozygous A18V variant in VLDLR that appears to be associated with a previously undescribed phenotype.

Keywords: clinic; diagnosis; genome; sequencing.

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Figures

Fig. 1
Fig. 1
Decision tree for 57 cases. The case review team evaluated 57 cases submitted for whole genome sequencing. The disposition of the cases is shown.
Fig. 2
Fig. 2
Choice of incidental findings. This Venn diagram summarizes the choice of incidental findings that each of the families selected.
See this image and copyright information in PMC

References

    1. Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014;59(1):5–15. - PubMed
    1. Worthey E A, Mayer A N, Syverson G D. et al.Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011;13(3):255–262. - PubMed
    1. Gahl W A, Boerkoel C F, Boehm M. The NIH Undiagnosed Diseases Program: bonding scientists and clinicians. Dis Model Mech. 2012;5(1):3–5. - PMC - PubMed
    1. Gahl W A, Mulvihill J J, Toro C. et al.The NIH Undiagnosed Diseases Program and Network: applications to modern medicine. Mol Genet Metab. 2016;117(4):393–400. - PMC - PubMed
    1. Yang Y, Muzny D M, Xia F. et al.Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014;312(18):1870–1879. - PMC - PubMed