{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:05:27Z","timestamp":1784286327592,"version":"3.55.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"DOI":"10.1007\/s00431-026-07204-x","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:53:53Z","timestamp":1782863633000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alagille syndrome case series: five new variants and two large deletions"],"prefix":"10.1007","volume":"185","author":[{"given":"Fatma \u0130lknur","family":"Varol","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0433-5970","authenticated-orcid":false,"given":"\u015e\u00fckr\u00fc","family":"G\u00fcng\u00f6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1872-3138","authenticated-orcid":false,"given":"Cemal","family":"Ekici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3300-8020","authenticated-orcid":false,"given":"I\u0307brahim","family":"Tekedereli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8533-8446","authenticated-orcid":false,"given":"Mukadder Ay\u015fe","family":"Selimo\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0778-3163","authenticated-orcid":false,"given":"Sel\u00e7uk","family":"Erdo\u011fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-8076","authenticated-orcid":false,"given":"Emre","family":"G\u00f6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"issue":"15","key":"7204_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26157626","volume":"26","author":"R V\u00e1zquez-Frias","year":"2025","unstructured":"V\u00e1zquez-Frias R, Varela-Fascinetto G, Acosta-Rodr\u00edguez-Bueno CP, Consuelo A, Carrillo A, Reyes-Apodaca M et al (2025) A retrospective study of clinical and genetic features in a long-term cohort of Mexican children with Alagille syndrome. Int J Mol Sci 26(15):7626. https:\/\/doi.org\/10.3390\/ijms26157626","journal-title":"Int J Mol Sci"},{"issue":"12","key":"7204_CR2","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1136\/jmg.40.12.891","volume":"40","author":"BM Kamath","year":"2003","unstructured":"Kamath BM, Bason L, Piccoli DA, Krantz ID, Spinner NB (2003) Consequences of JAG1 mutations. J Med Genet 40(12):891\u2013895","journal-title":"J Med Genet"},{"issue":"5","key":"7204_CR3","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/humu.20310","volume":"27","author":"DM Warthen","year":"2006","unstructured":"Warthen DM, Moore EC, Kamath BM, Morrissette JJ, Sanchez-Lara PA, Piccoli DA et al (2006) Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 27(5):436\u2013443. https:\/\/doi.org\/10.1002\/humu.20310","journal-title":"Hum Mutat"},{"issue":"1 Pt 3","key":"7204_CR4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.gene.2015.10.065","volume":"576","author":"CM Grochowski","year":"2016","unstructured":"Grochowski CM, Loomes KM, Spinner NB (2016) Jagged1 (JAG1): structure, expression, and disease associations. Gene 576(1 Pt 3):381\u2013384. https:\/\/doi.org\/10.1016\/j.gene.2015.10.065","journal-title":"Gene"},{"issue":"3","key":"7204_CR5","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/ng0797-235","volume":"16","author":"T Oda","year":"1997","unstructured":"Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A et al (1997) Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet 16(3):235\u2013242. https:\/\/doi.org\/10.1038\/ng0797-235","journal-title":"Nat Genet"},{"issue":"1\u20133","key":"7204_CR6","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.febslet.2004.08.022","volume":"574","author":"C Guarnaccia","year":"2004","unstructured":"Guarnaccia C, Pintar A, Pongor S (2004) Exon 6 of human Jagged-1 encodes an autonomously folding unit. FEBS Lett 574(1\u20133):156\u2013160. https:\/\/doi.org\/10.1016\/j.febslet.2004.08.022","journal-title":"FEBS Lett"},{"key":"7204_CR7","first-page":"301","volume":"30","author":"D Alagille","year":"1969","unstructured":"Alagille D, Habib EC, Thomassin NJ (1969) L\u2019atresie des voies biliaires intrahepatiques avec voies biliaires extrahepatiques permeables chez l\u2019enfant. J Pediatr Gastroenterol Nutr 30:301\u2013318","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"1","key":"7204_CR8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/ajmg.a.34369","volume":"158A","author":"BM Kamath","year":"2012","unstructured":"Kamath BM, Podkameni G, Hutchinson AL, Leonard LD, Gerfen J, Krantz ID et al (2012) Renal anomalies in Alagille syndrome: a disease-defining feature. Am J Med Genet A 158A(1):85\u201389. https:\/\/doi.org\/10.1002\/ajmg.a.34369","journal-title":"Am J Med Genet A"},{"issue":"11","key":"7204_CR9","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1161\/01.CIR.0000121361.01862.A4","volume":"109","author":"BM Kamath","year":"2004","unstructured":"Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA et al (2004) Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation 109(11):1354\u20131358. https:\/\/doi.org\/10.1161\/01.CIR.0000121361.01862.A4","journal-title":"Circulation"},{"issue":"3","key":"7204_CR10","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cld.2022.03.002","volume":"26","author":"MD Ayoub","year":"2022","unstructured":"Ayoub MD, Kamath BM (2022) Alagille syndrome: current understanding of pathogenesis and challenges in diagnosis and management. Clin Liver Dis 26(3):355\u2013370. https:\/\/doi.org\/10.1016\/j.cld.2022.03.002","journal-title":"Clin Liver Dis"},{"issue":"5","key":"7204_CR11","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1111\/liv.12920","volume":"36","author":"M Mouzaki","year":"2016","unstructured":"Mouzaki M, Bass LM, Sokol RJ, Piccoli DA, Quammie C, Loomes KM et al (2016) Early life predictive markers of liver disease outcome in an international, multicentre cohort of children with Alagille syndrome. Liver Int 36(5):755\u2013760. https:\/\/doi.org\/10.1111\/liv.12920","journal-title":"Liver Int"},{"issue":"4","key":"7204_CR12","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1097\/00005176-199910000-00011","volume":"29","author":"RE Quiros-Tejeira","year":"1999","unstructured":"Quiros-Tejeira RE, Ament ME, Heyman MB, Martin MG, Rosenthal P, Hall TR et al (1999) Variable morbidity in Alagille syndrome: a review of 43 cases. J Pediatr Gastroenterol Nutr 29(4):431\u2013437. https:\/\/doi.org\/10.1097\/00005176-199910000-00011","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"1","key":"7204_CR13","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1097\/MPG.0b013e3181f1572d","volume":"52","author":"P Subramaniam","year":"2011","unstructured":"Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB et al (2011) Diagnosis of Alagille syndrome: 25 years of experience at King\u2019s College Hospital. J Pediatr Gastroenterol Nutr 52(1):84\u201389. https:\/\/doi.org\/10.1097\/MPG.0b013e3181f1572d","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"2","key":"7204_CR14","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/ajmg.a.37429","volume":"170A","author":"K Izumi","year":"2016","unstructured":"Izumi K, Hayashi D, Grochowski CM, Kubota N, Nishi E, Arakawa M et al (2016) Discordant clinical phenotype in monozygotic twins with Alagille syndrome: possible influence of non-genetic factors. Am J Med Genet A 170A(2):471\u2013475. https:\/\/doi.org\/10.1002\/ajmg.a.37429","journal-title":"Am J Med Genet A"},{"issue":"12","key":"7204_CR15","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1002\/humu.23879","volume":"40","author":"MA Gilbert","year":"2019","unstructured":"Gilbert MA, Bauer RC, Rajagopalan R, Grochowski CM, Chao G, McEldrew D et al (2019) Alagille syndrome mutation update: comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification. Hum Mutat 40(12):2197\u20132220. https:\/\/doi.org\/10.1002\/humu.23879","journal-title":"Hum Mutat"},{"key":"7204_CR16","unstructured":"WHO. Child growth standards. Available at: https:\/\/www.who.int\/tools\/child-growth-standards. Accessed 2025"},{"issue":"5","key":"7204_CR17","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants. Genet Med 17(5):405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30","journal-title":"Genet Med"},{"key":"7204_CR18","unstructured":"Online Mendelian Inheritance in Man (OMIM). Available at: https:\/\/omim.org. Accessed 2025"},{"key":"7204_CR19","unstructured":"Human Gene Mutation Database (HGMD). Available at: http:\/\/www.hgmd.org. Accessed 2025"},{"key":"7204_CR20","unstructured":"ClinVar. Available at: https:\/\/www.ncbi.nlm.nih.gov\/clinvar. Accessed 2025"},{"key":"7204_CR21","unstructured":"Franklin by Genoox. Available at: https:\/\/franklin.genoox.com. Accessed 2025"},{"key":"7204_CR22","unstructured":"gnomAD. Available at: https:\/\/gnomad.broadinstitute.org. Accessed 2025"},{"key":"7204_CR23","unstructured":"PubMed. Available at: https:\/\/pubmed.ncbi.nlm.nih.gov. Accessed 2025"},{"key":"7204_CR24","unstructured":"VarSome. Available at: https:\/\/varsome.com. Accessed 2025"},{"key":"7204_CR25","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.semcdb.2012.01.010","volume":"23","author":"AL Penton","year":"2012","unstructured":"Penton AL, Leonard LD, Spinner NB (2012) Notch signaling in human development and disease. Semin Cell Dev Biol 23:450\u2013457","journal-title":"Semin Cell Dev Biol"},{"key":"7204_CR26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1006\/bbrc.2000.3469","volume":"276","author":"K Shimizu","year":"2000","unstructured":"Shimizu K, Chiba S, Saito T, Kumano K, Hirai H (2000) Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and Notch3 receptors. Biochem Biophys Res Commun 276:385\u2013389","journal-title":"Biochem Biophys Res Commun"},{"key":"7204_CR27","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/1098-1004(2001)17:1<18::AID-HUMU3>3.0.CO;2-T","volume":"17","author":"NB Spinner","year":"2001","unstructured":"Spinner NB, Colliton RP, Crosnier C, Krantz ID, Hadchouel M, Meunier-Rotival M (2001) Jagged1 mutations in Alagille syndrome. Hum Mutat 17:18\u201333","journal-title":"Hum Mutat"},{"issue":"2","key":"7204_CR28","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0022-3476(87)80153-1","volume":"110","author":"D Alagille","year":"1987","unstructured":"Alagille D, Estrada A, Hadchouel M, Gautier M, Odi\u00e8vre M, Dommergues JP (1987) Syndromic paucity of interlobular bile ducts: review of 80 cases. J Pediatr 110(2):195\u2013200","journal-title":"J Pediatr"},{"issue":"6","key":"7204_CR29","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1002\/j.1536-4801.1987.tb09426.x","volume":"6","author":"A Deprettere","year":"1987","unstructured":"Deprettere A, Portmann B, Mowat AP (1987) Syndromic paucity of the intrahepatic bile ducts. J Pediatr Gastroenterol Nutr 6(6):865\u2013871","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"3","key":"7204_CR30","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1002\/hep.510290331","volume":"29","author":"KM Emerick","year":"1999","unstructured":"Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA (1999) Features of Alagille syndrome in 92 patients. Hepatology 29(3):822\u2013829","journal-title":"Hepatology"},{"issue":"4","key":"7204_CR31","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1055\/s-0041-1730951","volume":"41","author":"TJ Kohut","year":"2021","unstructured":"Kohut TJ, Gilbert MA, Loomes KM (2021) Alagille syndrome: a focused review. Semin Liver Dis 41(4):525\u2013537","journal-title":"Semin Liver Dis"},{"key":"7204_CR32","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1161\/01.CIR.0000037221.45902.69","volume":"106","author":"DB McElhinney","year":"2002","unstructured":"McElhinney DB, Krantz ID, Bason L, Piccoli DA, Emerick KM, Spinner NB et al (2002) Cardiovascular phenotype and genotype-phenotype correlation in Alagille syndrome. Circulation 106:2567\u20132574","journal-title":"Circulation"},{"issue":"2","key":"7204_CR33","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/S0161-6420(99)90072-6","volume":"106","author":"M Hingorani","year":"1999","unstructured":"Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ et al (1999) Ocular abnormalities in Alagille syndrome. Ophthalmology 106(2):330\u2013337","journal-title":"Ophthalmology"},{"issue":"12","key":"7204_CR34","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1002\/jgh3.12830","volume":"6","author":"CM Chiang","year":"2022","unstructured":"Chiang CM, Jeng YM, Ho MC, Lai MW, Li HY, Chen PL et al (2022) Different clinical and genetic features of Alagille patients. JGH Open 6(12):839\u2013845","journal-title":"JGH Open"},{"key":"7204_CR35","unstructured":"Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A (eds) GeneReviews\u00ae\u00a0[Internet]. University of Washington, Seattle, Seattle (WA), pp 1993\u20132026"},{"issue":"6","key":"7204_CR36","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1891\/0730-0832.36.6.343","volume":"36","author":"D Jesina","year":"2017","unstructured":"Jesina D (2017) Alagille syndrome: an overview. Neonatal Netw 36(6):343\u2013347","journal-title":"Neonatal Netw"},{"key":"7204_CR37","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2147\/TACG.S86420","volume":"9","author":"M Saleh","year":"2016","unstructured":"Saleh M, Kamath BM, Chitayat D (2016) Alagille syndrome: clinical perspectives. Appl Clin Genet 9:75\u201382","journal-title":"Appl Clin Genet"},{"issue":"3","key":"7204_CR38","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s13353-014-0212-2","volume":"55","author":"D Jurkiewicz","year":"2014","unstructured":"Jurkiewicz D, Gliwicz D, Ciara E, Gerfen J, Pelc M, Piekutowska-Abramczuk D et al (2014) Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome. J Appl Genet 55(3):329\u2013336. https:\/\/doi.org\/10.1007\/s13353-014-0212-2","journal-title":"J Appl Genet"},{"issue":"3","key":"7204_CR39","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/humu.9313","volume":"25","author":"D Jurkiewicz","year":"2005","unstructured":"Jurkiewicz D, Popowska E, Gl\u00e4ser C, Hansmann I, Krajewska-Walasek M (2005) Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients. Hum Mutat 25(3):321. https:\/\/doi.org\/10.1002\/humu.9313","journal-title":"Hum Mutat"},{"issue":"1","key":"7204_CR40","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/ajmg.10652","volume":"112","author":"A Raas-Rothschild","year":"2002","unstructured":"Raas-Rothschild A, Shteyer E, Lerer I, Nir A, Granot E, Rein AJ (2002) Jagged1 gene mutation for abdominal coarctation of the aorta in Alagille syndrome. Am J Med Genet 112(1):75\u201378. https:\/\/doi.org\/10.1002\/ajmg.10652","journal-title":"Am J Med Genet"},{"issue":"1","key":"7204_CR41","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.gene.2012.02.038","volume":"499","author":"H Wang","year":"2012","unstructured":"Wang H, Wang X, Li Q, Chen S, Liu L, Wei Z et al (2012) Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome. Gene 499(1):191\u2013193. https:\/\/doi.org\/10.1016\/j.gene.2012.02.038","journal-title":"Gene"},{"issue":"5","key":"7204_CR42","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1034\/j.1399-0004.2001.590506.x","volume":"59","author":"ZR Yuan","year":"2001","unstructured":"Yuan ZR, Okaniwa M, Nagata I, Tazawa Y, Ito M, Kawarazaki H et al (2001) The DSL domain in mutant JAG1 ligand is essential for the severity of the liver defect in Alagille syndrome. Clin Genet 59(5):330\u2013337. https:\/\/doi.org\/10.1034\/j.1399-0004.2001.590506.x","journal-title":"Clin Genet"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07204-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-026-07204-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07204-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:25:52Z","timestamp":1784283952000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-026-07204-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["7204"],"URL":"https:\/\/doi.org\/10.1007\/s00431-026-07204-x","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"25 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the \u0130n\u00f6n\u00fc University Clinical Research Ethics Committee (Approval No: 2025\/8664) and conducted in accordance with the Declaration of Helsinki.","order":1,"name":"Ethics","label":"Ethics statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"542"}}