{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:09:18Z","timestamp":1792001358501,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T00:00:00Z","timestamp":1651881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/diagnostics12051169","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T08:04:21Z","timestamp":1651997061000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis"],"prefix":"10.3390","volume":"12","author":[{"given":"Marion","family":"Almes","sequence":"first","affiliation":[{"name":"Pediatric Hepatology and Pediatric Liver Transplant Unit, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, ERN RARE LIVER, Bic\u00eatre Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR-S 1193, Paris-Saclay University, H\u00e9patinov, 91400 Orsay, France"},{"name":"Plateforme d\u2019Expertise Maladies Rares Paris-Saclay, AP-HP, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Spraul","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 1193, Paris-Saclay University, H\u00e9patinov, 91400 Orsay, France"},{"name":"Plateforme d\u2019Expertise Maladies Rares Paris-Saclay, AP-HP, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Biochemistry Unit, DMU15, Bic\u00eatre Hospital, AP-HP, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Bron Hospital, 69677 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Girard","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Necker Hospital, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Roquelaure","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Marseille University Hospital, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolwenn","family":"Laborde","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Toulouse Hospital, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5290-0436","authenticated-orcid":false,"given":"Fr\u00e9deric","family":"Gottrand","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Univ. Lille, CHU Lille, INSERM U1286, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Turquet","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Saint-Denis Hospital, 97405 La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5777-8492","authenticated-orcid":false,"given":"Thierry","family":"Lamireau","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Bordeaux Hospital, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Dabadie","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Rennes Hospital, 35033 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Bonneton","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Nancy Hospital, 54035 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Thebaut","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology and Pediatric Liver Transplant Unit, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, ERN RARE LIVER, Bic\u00eatre Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR-S 1193, Paris-Saclay University, H\u00e9patinov, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babara","family":"Rohmer","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Bron Hospital, 69677 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lacaille","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Necker Hospital, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Brou\u00e9","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Toulouse Hospital, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-6437","authenticated-orcid":false,"given":"Alexandre","family":"Fabre","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Marseille University Hospital, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Mention-Mulliez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Univ. Lille, CHU Lille, INSERM U1286, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Bouligand","sequence":"additional","affiliation":[{"name":"Plateforme d\u2019Expertise Maladies Rares Paris-Saclay, AP-HP, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Molecular Genetics, Pharmacology and Hormonology Unit, Bic\u00eatre Hospital, AP-HP, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR 1185, Endocrine Physiology and Physiopathology, Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jacquemin","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology and Pediatric Liver Transplant Unit, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, ERN RARE LIVER, Bic\u00eatre Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR-S 1193, Paris-Saclay University, H\u00e9patinov, 91400 Orsay, France"},{"name":"Plateforme d\u2019Expertise Maladies Rares Paris-Saclay, AP-HP, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-3193","authenticated-orcid":false,"given":"Emmanuel","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology and Pediatric Liver Transplant Unit, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, ERN RARE LIVER, Bic\u00eatre Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris-Saclay University, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"INSERM UMR-S 1193, Paris-Saclay University, H\u00e9patinov, 91400 Orsay, France"},{"name":"Plateforme d\u2019Expertise Maladies Rares Paris-Saclay, AP-HP, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1001\/jama.2020.0837","article-title":"Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements","volume":"323","author":"Harpavat","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/MPG.0000000000001334","article-title":"Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition","volume":"64","author":"Fawaz","year":"2017","journal-title":"J. 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