{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:39:06Z","timestamp":1792795146866,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,13]],"date-time":"2019-10-13T00:00:00Z","timestamp":1570924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The <jats:italic>ABCC2<\/jats:italic> gene is implicated in Dubin\u2010Johnson syndrome (DJS), a rare autosomal recessive liver disorder. The primary aim of this study was to determine the diagnostic value of <jats:italic>ABCC2<\/jats:italic> genetic testing in the largest cohort of DJS reported to date. The high number of patients with cholestatic manifestations in this series prompted us to evaluate the genetic contribution of rare, potentially pathogenic <jats:italic>ABCC2<\/jats:italic> variants to other inherited cholestatic disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cohort study included 32 patients with clinical DJS diagnosis, and 372 patients referred for the following disorders: low phospholipid\u2010associated cholelithiasis (LPAC) syndrome, intrahepatic cholestasis of pregnancy (ICP) and benign recurrent intrahepatic cholestasis (BRIC). <jats:italic>ABCC2<\/jats:italic> was screened by next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Most patients with clinical DJS had positive genetic diagnosis (n\u00a0=\u00a030; 94%), with a great diversity of point mutations and copy number variations in <jats:italic>ABCC2<\/jats:italic>. Strikingly, eight (27%) of these patients showed transient cholestatic features at presentation: four neonatal cholestasis, two ICP, one contraceptive\u2010induced cholestasis and one sporadic cholestasis. Conversely, the frequency of rare, heterozygous, potentially pathogenic <jats:italic>ABCC2<\/jats:italic> variants in patients with LPAC, ICP or BRIC did not differ significantly from that of the general population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This large series reveals that DJS is a highly homogeneous Mendelian disorder involving a large spectrum of <jats:italic>ABCC2<\/jats:italic> variants. Genetic testing is crucial to establish early DJS diagnosis in patients with atypical presentations, such as neonatal cholestasis. This study also provides no evidence for the contribution of rare, potentially pathogenic <jats:italic>ABCC2<\/jats:italic> variants to other inherited cholestatic disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14260","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T06:58:56Z","timestamp":1569221936000},"page":"163-174","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Genetic contribution of <i>ABCC2<\/i> to Dubin\u2010Johnson syndrome and inherited cholestatic disorders"],"prefix":"10.1111","volume":"40","author":[{"given":"Christophe","family":"Corpechot","sequence":"first","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Inflammatoires des Voies Biliaires et des H\u00e9patites Auto\u2010Immunes (MIVB\u2010H) Fili\u00e8re de Sant\u00e9 des Maladies Rares du Foie de l'enfant et de l'adulte (FILFOIE) Assistance Publique\u2010H\u00f4pitaux de Paris 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