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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
1   HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
Pamela C. Fraser
2   Aerodigestive and Genomic Services, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
Michael F. Gutzeit
3   Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
Jeremy M. Harris
4   Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
Tina M. Hambuch
5   Pediatric Genetics, Invitae Corporation, San Francisco, California, United States
,
Daniel C. Helbling
6   Human Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Howard J. Jacob
1   HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
Juliet N. Kersten
3   Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
Steven R. Leuthner
7   Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Thomas May
1   HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
8   University of California, San Francisco, California, United States
,
Paula E. North
7   Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Sasha Z. Prisco
9   Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States
,
Bryce A. Schuler
10   Medical Scientist Training Program, Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Mary Shimoyama
11   Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Kimberly A. Strong
12   Ethics and Genomics Program, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
Scott K. Van Why
13   Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Regan Veith
14   Genetics Department, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, United States
,
James Verbsky
15   Division of Rheumatology, Department of Pediatrics, CIRL and Clinical and Translational Research, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Arthur M. Weborg Jr.
4   Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
Brandon M. Wilk
4   Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
Rodney E. Willoughby Jr.
16   Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
Elizabeth A. Worthey
4   Software Development and Informatics, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States
,
David P. Dimmock
17   Rady Children's Institute for Genomic Medicine, San Diego, California, United States
› Author Affiliations
Further Information

Publication History

08 August 2016

02 October 2016

Publication Date:
28 November 2016 (online)

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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

Supplementary Material

 

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