{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:07:23Z","timestamp":1789470443474,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cholestasis is caused by genetic disorders in 25% of cases. Our study aimed to describe the clinical and genetic profile of cholestasis and to demonstrate the importance of next\u2010generation sequencing (NGS) in the etiologic diagnosis of genetic cholestasis. We included patients referred for cholestasis over a 10\u2010year period. Molecular studies using NGS consisted of a 292\u2010gene panel and\/or whole exome sequencing. Our cohort included 70 patients from 66 unrelated families. A genetic diagnosis was established in 70% of the families. The most common diagnoses were Type 2 progressive familial intrahepatic cholestasis (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912), neonatal sclerosing cholangitis (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), low phospholipid\u2010associated cholelithiasis syndrome (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094), and Alagille syndrome (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094). The\n                    <jats:italic>ABCB11<\/jats:italic>\n                    gene was most frequently mutated (15\/46), with two recurrent variants, c.1062T&gt;A (p.Tyr354*) and c.1826_1827dup (p.Ile610Glnfs*45), found in six and four families, respectively. Our results showed a 62% diagnostic yield of molecular testing using NGS in cholestasis. An accurate diagnosis was key to providing appropriate genetic counseling, guiding screening of variant carriers, and prenatal diagnosis.\n                  <\/jats:p>","DOI":"10.1111\/cge.70242","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:54:45Z","timestamp":1789469685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Spectrum of Cholestasis in Tunisia and Diagnostic Yield of Next\u2010Generation Sequencing: Case Series of 70 Patients"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2535-5309","authenticated-orcid":false,"given":"Amal","family":"Abdmouleh","sequence":"first","affiliation":[{"name":"Genetic Department Mongi Slim Hospital  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-0294","authenticated-orcid":false,"given":"Houweyda","family":"Jilani","sequence":"additional","affiliation":[{"name":"Genetic Department Mongi Slim Hospital  Tunis Tunisia"},{"name":"Research Laboratory LR22SP01 Mongi Slim Hospital  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-1910","authenticated-orcid":false,"given":"Imen","family":"Rejeb","sequence":"additional","affiliation":[{"name":"Genetic Department Mongi Slim Hospital  Tunis Tunisia"},{"name":"Research Laboratory LR22SP01 Mongi Slim Hospital  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syrine","family":"Hizem","sequence":"additional","affiliation":[{"name":"Genetic Department Mongi Slim Hospital  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"},{"name":"Human Genetics Laboratory, LR99ES10 \u2010 Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-6286","authenticated-orcid":false,"given":"Nicolas","family":"Pottier","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille Institut Pasteur de Lille, UMR9020 CNRS \u2010 U1277 Inserm \u2013 CANTHER  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Larrue","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille Institut Pasteur de Lille, UMR9020 CNRS \u2010 U1277 Inserm \u2013 CANTHER  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Arondal","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille Institut Pasteur de Lille, UMR9020 CNRS \u2010 U1277 Inserm \u2013 CANTHER  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Hanquet","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille Institut Pasteur de Lille, UMR9020 CNRS \u2010 U1277 Inserm \u2013 CANTHER  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2674-6049","authenticated-orcid":false,"given":"Rania","family":"Benrabeh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"},{"name":"Pediatric Department C Children's Hospital Bechir Hamza  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olfa","family":"Bouyahia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"},{"name":"Pediatric Department C Children's Hospital Bechir Hamza  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Mazigh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"},{"name":"Pediatric Department C Children's Hospital Bechir Hamza  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3031-4783","authenticated-orcid":false,"given":"Yasmina","family":"Elaribi","sequence":"additional","affiliation":[{"name":"Genetic Department Mongi Slim Hospital  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"},{"name":"Research Laboratory LR16SP01 \u201cInfertility and Oncofertility\u201d Aziza Othmana Hospital  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamia","family":"Benjemaa","sequence":"additional","affiliation":[{"name":"Genetic Department Mongi Slim Hospital  Tunis Tunisia"},{"name":"Research Laboratory LR22SP01 Mongi Slim Hospital  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcg.0000155551.37266.26"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001334"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12111837"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0132-z"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"128","article-title":"Cholestasis in Infants: A Study of the Children's Hospital of Tunisia","volume":"86","author":"Bouyahia O.","year":"2008","journal-title":"La Tunisie 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With Normal GammaglutamylTransferasis From Management to Molecular Investigation With Novel Mutations in ATP8B1 and ABCB11: Tunisian Study","volume":"2","author":"Barkaoui E.","year":"2018","journal-title":"Journal of Genetic Disorders"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.07.004"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145021"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.09.028"}],"container-title":["Clinical 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