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Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis

Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this...

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Autores principales: Almes, Marion, Spraul, Anne, Ruiz, Mathias, Girard, Muriel, Roquelaure, Bertrand, Laborde, Nolwenn, Gottrand, Fréderic, Turquet, Anne, Lamireau, Thierry, Dabadie, Alain, Bonneton, Marjorie, Thebaut, Alice, Rohmer, Babara, Lacaille, Florence, Broué, Pierre, Fabre, Alexandre, Mention-Mulliez, Karine, Bouligand, Jérôme, Jacquemin, Emmanuel, Gonzales, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140938/
https://www.ncbi.nlm.nih.gov/pubmed/35626323
http://dx.doi.org/10.3390/diagnostics12051169
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author Almes, Marion
Spraul, Anne
Ruiz, Mathias
Girard, Muriel
Roquelaure, Bertrand
Laborde, Nolwenn
Gottrand, Fréderic
Turquet, Anne
Lamireau, Thierry
Dabadie, Alain
Bonneton, Marjorie
Thebaut, Alice
Rohmer, Babara
Lacaille, Florence
Broué, Pierre
Fabre, Alexandre
Mention-Mulliez, Karine
Bouligand, Jérôme
Jacquemin, Emmanuel
Gonzales, Emmanuel
author_facet Almes, Marion
Spraul, Anne
Ruiz, Mathias
Girard, Muriel
Roquelaure, Bertrand
Laborde, Nolwenn
Gottrand, Fréderic
Turquet, Anne
Lamireau, Thierry
Dabadie, Alain
Bonneton, Marjorie
Thebaut, Alice
Rohmer, Babara
Lacaille, Florence
Broué, Pierre
Fabre, Alexandre
Mention-Mulliez, Karine
Bouligand, Jérôme
Jacquemin, Emmanuel
Gonzales, Emmanuel
author_sort Almes, Marion
collection PubMed
description Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. Methods: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). Results: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. Conclusions: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations.
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spelling pubmed-91409382022-05-28 Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis Almes, Marion Spraul, Anne Ruiz, Mathias Girard, Muriel Roquelaure, Bertrand Laborde, Nolwenn Gottrand, Fréderic Turquet, Anne Lamireau, Thierry Dabadie, Alain Bonneton, Marjorie Thebaut, Alice Rohmer, Babara Lacaille, Florence Broué, Pierre Fabre, Alexandre Mention-Mulliez, Karine Bouligand, Jérôme Jacquemin, Emmanuel Gonzales, Emmanuel Diagnostics (Basel) Article Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. Methods: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). Results: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. Conclusions: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations. MDPI 2022-05-07 /pmc/articles/PMC9140938/ /pubmed/35626323 http://dx.doi.org/10.3390/diagnostics12051169 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Almes, Marion
Spraul, Anne
Ruiz, Mathias
Girard, Muriel
Roquelaure, Bertrand
Laborde, Nolwenn
Gottrand, Fréderic
Turquet, Anne
Lamireau, Thierry
Dabadie, Alain
Bonneton, Marjorie
Thebaut, Alice
Rohmer, Babara
Lacaille, Florence
Broué, Pierre
Fabre, Alexandre
Mention-Mulliez, Karine
Bouligand, Jérôme
Jacquemin, Emmanuel
Gonzales, Emmanuel
Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
title Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
title_full Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
title_fullStr Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
title_full_unstemmed Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
title_short Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
title_sort targeted-capture next-generation sequencing in diagnosis approach of pediatric cholestasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140938/
https://www.ncbi.nlm.nih.gov/pubmed/35626323
http://dx.doi.org/10.3390/diagnostics12051169
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