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

Authors :
Marion Almes
Anne Spraul
Mathias Ruiz
Muriel Girard
Bertrand Roquelaure
Nolwenn Laborde
Fréderic Gottrand
Anne Turquet
Thierry Lamireau
Alain Dabadie
Marjorie Bonneton
Alice Thebaut
Babara Rohmer
Florence Lacaille
Pierre Broué
Alexandre Fabre
Karine Mention-Mulliez
Jérôme Bouligand
Emmanuel Jacquemin
Emmanuel Gonzales
Source :
Diagnostics, Vol 12, Iss 5, p 1169 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
20754418
Volume :
12
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Diagnostics
Publication Type :
Academic Journal
Accession number :
edsdoj.71ba909fe65b4bb7be1a22d10e514f3b
Document Type :
article
Full Text :
https://doi.org/10.3390/diagnostics12051169