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Abstract Details
Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis
Diagnostics (Basel). 2022 May 7;12(5):1169. doi: 10.3390/diagnostics12051169.
1Pediatric Hepatology and Pediatric Liver Transplant Unit, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, ERN RARE LIVER, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris-Saclay University, 94270 Le Kremlin-Bicêtre, France.
2INSERM UMR-S 1193, Paris-Saclay University, Hépatinov, 91400 Orsay, France.
3Plateforme d'Expertise Maladies Rares Paris-Saclay, AP-HP, 94270 Le Kremlin-Bicêtre, France.
4Biochemistry Unit, DMU15, Bicêtre Hospital, AP-HP, Paris-Saclay University, 94270 Le Kremlin-Bicêtre, France.
5Pediatric Gastroenterology, Hepatology and Nutrition Unit, Bron Hospital, 69677 Lyon, France.
6Pediatric Gastroenterology, Hepatology and Nutrition Unit, Necker Hospital, 75015 Paris, France.
7Pediatric Gastroenterology, Hepatology and Nutrition Unit, Marseille University Hospital, 13288 Marseille, France.
8Pediatric Gastroenterology, Hepatology and Nutrition Unit, Toulouse Hospital, 31300 Toulouse, France.
9Department of Pediatric Gastroenterology Hepatology and Nutrition, Univ. Lille, CHU Lille, INSERM U1286, 59000 Lille, France.
10Pediatric Gastroenterology, Hepatology and Nutrition Unit, Saint-Denis Hospital, 97405 La Réunion, France.
11Pediatric Gastroenterology, Hepatology and Nutrition Unit, Bordeaux Hospital, 33076 Bordeaux, France.
12Pediatric Gastroenterology, Hepatology and Nutrition Unit, Rennes Hospital, 35033 Rennes, France.
13Pediatric Gastroenterology, Hepatology and Nutrition Unit, Nancy Hospital, 54035 Nancy, France.
14Molecular Genetics, Pharmacology and Hormonology Unit, Bicêtre Hospital, AP-HP, Paris-Saclay University, 94270 Le Kremlin-Bicêtre, France.
15INSERM UMR 1185, Endocrine Physiology and Physiopathology, Paris-Saclay University, 94270 Le Kremlin-Bicêtre, France.
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.
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