Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease

Objective. Wilson’s disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-sa...

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Main Authors: Dániel Németh, Kristóf Árvai, Péter Horváth, János Pál Kósa, Bálint Tobiás, Bernadett Balla, Anikó Folhoffer, Anna Krolopp, Péter András Lakatos, Ferenc Szalay
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2016/4548039
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author Dániel Németh
Kristóf Árvai
Péter Horváth
János Pál Kósa
Bálint Tobiás
Bernadett Balla
Anikó Folhoffer
Anna Krolopp
Péter András Lakatos
Ferenc Szalay
author_facet Dániel Németh
Kristóf Árvai
Péter Horváth
János Pál Kósa
Bálint Tobiás
Bernadett Balla
Anikó Folhoffer
Anna Krolopp
Péter András Lakatos
Ferenc Szalay
author_sort Dániel Németh
collection DOAJ
description Objective. Wilson’s disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-saving, cost-effective method for full sequencing of the whole ATP7B gene compared to the traditional Sanger sequencing. This is the first report on the clinical use of NGS to examine ATP7B gene. Materials and Methods. We used Ion Torrent Personal Genome Machine in four heterozygous patients for the identification of the other mutations and also in two patients with no known mutation. One patient with acute on chronic liver failure was a candidate for acute liver transplantation. The results were validated by Sanger sequencing. Results. In each case, the diagnosis of Wilson’s disease was confirmed by identifying the mutations in both alleles within 48 hours. One novel mutation (p.Ala1270Ile) was found beyond the eight other known ones. The rapid detection of the mutations made possible the prompt diagnosis of WD in a patient with acute liver failure. Conclusions. According to our results we found next-generation sequencing a very useful, reliable, time-saving, and cost-effective method for diagnosing Wilson’s disease in selected cases.
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spelling doaj-art-26f9d746bdb347b389422ef8fe2cb9a12025-08-20T02:04:24ZengWileyGastroenterology Research and Practice1687-61211687-630X2016-01-01201610.1155/2016/45480394548039Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s DiseaseDániel Németh0Kristóf Árvai1Péter Horváth2János Pál Kósa3Bálint Tobiás4Bernadett Balla5Anikó Folhoffer6Anna Krolopp7Péter András Lakatos8Ferenc Szalay91st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, HungaryPentaCore Lab, Koranyi Sandor Street 2/a, Budapest 1083, Hungary1st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, Hungary1st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, HungaryPentaCore Lab, Koranyi Sandor Street 2/a, Budapest 1083, HungaryPentaCore Lab, Koranyi Sandor Street 2/a, Budapest 1083, Hungary1st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, Hungary1st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, Hungary1st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, Hungary1st Department of Internal Medicine, Semmelweis University, Koranyi Sandor Street 2/a, Budapest 1083, HungaryObjective. Wilson’s disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-saving, cost-effective method for full sequencing of the whole ATP7B gene compared to the traditional Sanger sequencing. This is the first report on the clinical use of NGS to examine ATP7B gene. Materials and Methods. We used Ion Torrent Personal Genome Machine in four heterozygous patients for the identification of the other mutations and also in two patients with no known mutation. One patient with acute on chronic liver failure was a candidate for acute liver transplantation. The results were validated by Sanger sequencing. Results. In each case, the diagnosis of Wilson’s disease was confirmed by identifying the mutations in both alleles within 48 hours. One novel mutation (p.Ala1270Ile) was found beyond the eight other known ones. The rapid detection of the mutations made possible the prompt diagnosis of WD in a patient with acute liver failure. Conclusions. According to our results we found next-generation sequencing a very useful, reliable, time-saving, and cost-effective method for diagnosing Wilson’s disease in selected cases.http://dx.doi.org/10.1155/2016/4548039
spellingShingle Dániel Németh
Kristóf Árvai
Péter Horváth
János Pál Kósa
Bálint Tobiás
Bernadett Balla
Anikó Folhoffer
Anna Krolopp
Péter András Lakatos
Ferenc Szalay
Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease
Gastroenterology Research and Practice
title Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease
title_full Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease
title_fullStr Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease
title_full_unstemmed Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease
title_short Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease
title_sort clinical use of next generation sequencing in the diagnosis of wilson s disease
url http://dx.doi.org/10.1155/2016/4548039
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