Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis.
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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.
SUBMITTER: Almes M
PROVIDER: S-EPMC9140938 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis.
Almes Marion M Spraul Anne A Ruiz Mathias M Girard Muriel M Roquelaure Bertrand B Laborde Nolwenn N Gottrand Fréderic F Turquet Anne A Lamireau Thierry T Dabadie Alain A Bonneton Marjorie M Thebaut Alice A Rohmer Babara B Lacaille Florence F Broué Pierre P Fabre Alexandre A Mention-Mulliez Karine K Bouligand Jérôme J Jacquemin Emmanuel E Gonzales Emmanuel E
Diagnostics (Basel, Switzerland) 20220507 5
<h4>Background</h4>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.<h4>Methods</h4>Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targe ...[more]
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