Exome sequencing of an adolescent with nonalcoholic fatty liver disease identifies a clinically actionable case of Wilson disease.

Cold Spring Harbor Molecular Case Studies
Julia WattacherilDavid B Goldstein

Abstract

Diagnostic whole-exome sequencing has proven highly successful in a range of rare diseases, particularly early-onset genetic conditions. In more common conditions, however, exome sequencing for diagnostic purposes remains the exception. Here we describe a patient initially diagnosed with a common, complex liver disease, nonalcoholic fatty liver disease (NAFLD), who was determined to have Wilson disease (WD) upon research-related exome sequencing. The patient presented as a 14.5-yr-old adolescent with chronically elevated aminotransferases, normal ceruloplasmin, and histologic examination consistent with NAFLD with advanced fibrosis. He was enrolled in a large longitudinal study of patients with NAFLD and was found to have WD by exome sequencing performed 4 yr later. This new diagnosis, confirmed clinically by 24 h urine copper quantification, led to a change in the therapy from lifestyle counseling to directed treatment with d-penicillamine, a copper chelating agent. In this case, the likelihood of making the correct diagnosis and thereby choosing the appropriate treatment was increased by exome sequencing and careful interpretation. This example illustrates the utility of exome sequencing diagnostically in more common conditio...Continue Reading

References

Nov 1, 1991·Annals of Internal Medicine·W StremmelG Strohmeyer
Feb 1, 1995·Nature Genetics·G R ThomasD W Cox
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·A S PayneJ D Gitlin
Jan 15, 1999·European Journal of Human Genetics : EJHG·H H DucG Auburger
Mar 19, 2005·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Anil DhawanGiorgina Mieli-Vergani
Oct 4, 2006·Pediatrics·Jeffrey B SchwimmerCynthia Behling
May 29, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Eve A RobertsUNKNOWN American Association for Study of Liver Diseases (AASLD)
Oct 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Murim ChoiRichard P Lifton
Oct 20, 2010·Best Practice & Research. Clinical Gastroenterology·Dominik Huster
Dec 22, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Elizabeth A WortheyDavid P Dimmock
Jun 17, 2011·Science Translational Medicine·Matthew N BainbridgeRichard A Gibbs
Jun 29, 2012·Brain : a Journal of Neurology·Janel O JohnsonAndrew B Singleton
Nov 21, 2013·Brain : a Journal of Neurology·A Reghan FoleyHenry Houlden
Jun 6, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Alejandro IglesiasWendy K Chung
Jul 22, 2014·Annals of Neurology·David BeardenEthan M Goldberg
Sep 15, 2014·Nature Genetics·Neil RombergRichard P Lifton
Jan 16, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Xiaolin ZhuDavid B Goldstein
May 6, 2016·Cold Spring Harbor Molecular Case Studies·Slavé PetrovskiDavid B Goldstein
Nov 17, 2016·European Journal of Human Genetics : EJHG·Daniel TrujillanoRami Abou Jamra
Mar 24, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lisenka E L M VissersMichèl A A P Willemsen
Jul 18, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Naga ChalasaniArun J Sanyal
Nov 23, 2017·The New England Journal of Medicine·Anna M Diehl, Christopher Day

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Citations

Jun 9, 2020·F1000Research·Jennifer Vittorio, Joel E Lavine

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Methods Mentioned

BETA
biopsy
exome sequencing
nucleic acid purification

Software Mentioned

SnpEff
GenomeAnalysisToolKit
picard
BWA
- tools

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