{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:08:09Z","timestamp":1790348889558,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alagille syndrome (ALGS) is a multisystem condition characterized by cholestasis and bile duct paucity on liver biopsy and variable involvement of the heart, skeleton, eyes, kidneys, and face and caused by pathogenic variants in the JAG1 or NOTCH2 gene. The variable expressivity of the clinical phenotype and the lack of genotype\u2013phenotype correlations lead to significant diagnostic difficulties. Here we present an analysis of 18 patients with cholestasis who were diagnosed with ALGS. We used an NGS panel targeting coding exons of 52 genes, including the JAG1 and NOTCH2 genes. Sanger sequencing was used to verify the mutation in the affected individuals and family members. The specific facial phenotype was seen in 16\/18 (88.9%). Heart defects were seen in 8\/18 (44.4%) patients (pulmonary stenosis in 7\/8). Butterfly vertebrae were seen in 5\/14 (35.7%) patients. Renal involvement was detected in 2\/18 (11.1%) cases\u2014one patient had renal cysts, and one had obstructive hydronephrosis. An ophthalmology examination was performed on 12 children, and only one had posterior embryotoxon (8.3%). A percutaneous liver biopsy was performed in nine cases. Bile duct paucity was detected in six\/nine cases (66.7%). Two patients required liver transplantation because of cirrhosis. We identified nine novel variants in the JAG1 gene\u2014eight frameshift variants (c.1619_1622dupGCTA (p.Tyr541X), c.1160delG (p.Gly387fs), c.964dupT (p.C322fs), c.120delG (p.L40fs), c.1984dupG (p.Ala662Glyfs), c.3168_3169delAG (p.R1056Sfs*51), c.2688delG (p.896CysfsTer49), c.164dupG (p.Cys55fs)) and one missense variant, c.2806T &gt; G (p.Cys936Gly). None of the patients presented with NOTCH2 variants. In accordance with the classical criteria, only six patients could meet the diagnostic criteria in our cohort without genetic analysis. Genetic testing is important in the diagnosis of ALGS and can help differentiate it from other types of cholestasis.<\/jats:p>","DOI":"10.3390\/ijms241411758","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:47:03Z","timestamp":1690159623000},"page":"11758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical Characterization of Alagille Syndrome in Patients with Cholestatic Liver Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-045X","authenticated-orcid":false,"given":"Natalia","family":"Semenova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-0280","authenticated-orcid":false,"given":"Elena","family":"Kamenets","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Annenkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5118","authenticated-orcid":false,"given":"Andrey","family":"Marakhonov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gusarova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Demina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Guseva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Anisimova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0822-751X","authenticated-orcid":false,"given":"Anna","family":"Degtyareva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov, Ministry of Health of the Russian Federation, 115522 Moscow, Russia"},{"name":"Department of Neonatology, First Moscow State Medical University named after I.M. Sechenov, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Taran","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Strokova","sequence":"additional","affiliation":[{"name":"Federal Research Centre of Nutrition and Biotechnology, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0022-3476(75)80706-2","article-title":"Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur","volume":"86","author":"Alagille","year":"1975","journal-title":"J. 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