Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic

David Bick; Pamela C. Fraser; Michael F. Gutzeit; Jeremy M. Harris; Tina M. Hambuch; Daniel C. Helbling; Howard J. Jacob; Juliet N. Kersten; Steven R. Leuthner; Thomas May; Paula E. North; Sasha Z. Prisco; Bryce A. Schuler; Mary Shimoyama; Kimberly A. Strong; Scott K. Van Why; Regan Veith; James Verbsky; Arthur M. Weborg Jr.; Brandon M. Wilk; Rodney E. Willoughby Jr.; Elizabeth A. Worthey; David P. Dimmock

doi:10.1055/s-0036-1593968

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2017; 06(02): 061-076
DOI: 10.1055/s-0036-1593968

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic

David Bick

¹HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

Pamela C. Fraser

²Aerodigestive and Genomic Services, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States

,

Michael F. Gutzeit

³Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States

,

Jeremy M. Harris

⁴Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

Tina M. Hambuch

⁵Pediatric Genetics, Invitae Corporation, San Francisco, California, United States

,

Daniel C. Helbling

⁶Human Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Howard J. Jacob

¹HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

Juliet N. Kersten

³Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States

,

Steven R. Leuthner

⁷Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Thomas May

¹HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

⁸University of California, San Francisco, California, United States

,

Paula E. North

⁷Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Sasha Z. Prisco

⁹Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States

,

Bryce A. Schuler

¹⁰Medical Scientist Training Program, Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Mary Shimoyama

¹¹Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Kimberly A. Strong

¹²Ethics and Genomics Program, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

Scott K. Van Why

¹³Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Regan Veith

¹⁴Genetics Department, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, United States

,

James Verbsky

¹⁵Division of Rheumatology, Department of Pediatrics, CIRL and Clinical and Translational Research, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Arthur M. Weborg Jr.

⁴Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

Brandon M. Wilk

⁴Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

Rodney E. Willoughby Jr.

¹⁶Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

,

Elizabeth A. Worthey

⁴Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States

,

David P. Dimmock

¹⁷Rady Children's Institute for Genomic Medicine, San Diego, California, United States

› Author Affiliations

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

genome - sequencing - diagnosis - clinic

Full Text

References

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