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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9140938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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