Diagnostics (May 2022)

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

  • 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

DOI
https://doi.org/10.3390/diagnostics12051169
Journal volume & issue
Vol. 12, no. 5
p. 1169

Abstract

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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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