{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:33Z","timestamp":1791229653054,"version":"4.1.0"},"reference-count":103,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alagille syndrome (ALGS) is an autosomal dominant disorder caused by pathogenic variants in JAG1 or NOTCH2, which encode fundamental components of the Notch signaling pathway. Clinical features span multiple organ systems including hepatic, cardiac, vascular, renal, skeletal, craniofacial, and ocular, and occur with variable phenotypic penetrance. Genotype\u2013phenotype correlation studies have not yet shown associations between mutation type and clinical manifestations or severity, and it has been hypothesized that modifier genes may modulate the effects of JAG1 and NOTCH2 pathogenic variants. Medical management is supportive, focusing on clinical manifestations of disease, with liver transplant indicated for severe pruritus, liver synthetic dysfunction, portal hypertension, bone fractures, and\/or growth failure. New therapeutic approaches are under investigation, including ileal bile acid transporter (IBAT) inhibitors and other approaches that may involve targeted interventions to augment the Notch signaling pathway in involved tissues.<\/jats:p>","DOI":"10.1055\/s-0041-1730951","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T19:54:54Z","timestamp":1625255694000},"page":"525-537","source":"Crossref","is-referenced-by-count":87,"title":["Alagille Syndrome: A Focused Review on Clinical Features, Genetics, and Treatment"],"prefix":"10.1055","volume":"41","author":[{"given":"Taisa J.","family":"Kohut","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Loomes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"ref1","first-page":"301","article-title":"L'atresie des voies biliaires intrahepatiques avec voies biliaires extrahepatiques permeables chez l'enfant","author":"D Alagille","year":"1969","journal-title":"J Par Pediatr"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0022-3476(87)80153-1","article-title":"Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases","volume":"110","author":"D Alagille","year":"1987","journal-title":"J Pediatr"},{"issue":"06","key":"ref3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1136\/adc.48.6.459","article-title":"Arteriohepatic dysplasia: familial pulmonary arterial stenosis with neonatal liver disease","volume":"48","author":"G H Watson","year":"1973","journal-title":"Arch Dis Child"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1136\/jmg.40.12.891","article-title":"Consequences of JAG1 mutations","volume":"40","author":"B M Kamath","year":"2003","journal-title":"J Med Genet"},{"issue":"03","key":"ref5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/ng0797-243","article-title":"Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1","volume":"16","author":"L Li","year":"1997","journal-title":"Nat Genet"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ng0797-235","article-title":"Mutations in the human Jagged1 gene are responsible for Alagille syndrome","volume":"16","author":"T Oda","year":"1997","journal-title":"Nat Genet"},{"issue":"02","key":"ref7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41436-020-00989-8","article-title":"Genome sequencing increases diagnostic yield in clinically diagnosed Alagille syndrome patients with previously negative test results","volume":"23","author":"R Rajagopalan","year":"2021","journal-title":"Genet Med"},{"issue":"02","key":"ref8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1136\/jmedgenet-2011-100544","article-title":"NOTCH2 mutations in Alagille syndrome","volume":"49","author":"B M Kamath","year":"2012","journal-title":"J Med Genet"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1086\/505332","article-title":"NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway","volume":"79","author":"R McDaniell","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"12","key":"ref10","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1002\/humu.23879","article-title":"Alagille syndrome mutation update: Comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification","volume":"40","author":"M A Gilbert","year":"2019","journal-title":"Hum Mutat"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2147\/TACG.S86420","article-title":"Alagille syndrome: clinical perspectives","volume":"9","author":"M Saleh","year":"2016","journal-title":"Appl Clin Genet"},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/1098-1004(2001)17:1<18::AID-HUMU3>3.0.CO;2-T","article-title":"Jagged1 mutations in Alagille syndrome","volume":"17","author":"N B Spinner","year":"2001","journal-title":"Hum Mutat"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S0016-5085(99)70017-X","article-title":"Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome","volume":"116","author":"C Crosnier","year":"1999","journal-title":"Gastroenterology"},{"issue":"05","key":"ref14","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.jcmgh.2016.05.013","article-title":"THBS2 is a candidate modifier of liver disease severity in Alagille syndrome","volume":"2","author":"E A Tsai","year":"2016","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"06","key":"ref15","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1002\/hep.22538","article-title":"Bile duct proliferation in Jag1\/fringe heterozygous mice identifies candidate modifiers of the Alagille syndrome hepatic phenotype","volume":"48","author":"M J Ryan","year":"2008","journal-title":"Hepatology"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/hep.28024","article-title":"Jagged1 heterozygosity in mice results in a congenital cholangiopathy which is reversed by concomitant deletion of one copy of Poglut1 (Rumi)","volume":"63","author":"S M Thakurdas","year":"2016","journal-title":"Hepatology"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1002\/hep.30912","article-title":"Sox9 is a modifier of the liver disease severity in a mouse model of Alagille syndrome","volume":"71","author":"J M Adams","year":"2020","journal-title":"Hepatology"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/hep.510290331","article-title":"Features of Alagille syndrome in 92 patients: frequency and relation to prognosis","volume":"29","author":"K M Emerick","year":"1999","journal-title":"Hepatology"},{"issue":"01","key":"ref19","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/MPG.0b013e3181f1572d","article-title":"Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital","volume":"52","author":"P Subramaniam","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/gut.49.3.431","article-title":"Outcome of liver disease in children with Alagille syndrome: a study of 163 patients","volume":"49","author":"P Lykavieris","year":"2001","journal-title":"Gut"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1097\/MPG.0b013e3181cea48d","article-title":"A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome","volume":"50","author":"B M Kamath","year":"2010","journal-title":"J Pediatr Gastroenterol 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Pitfalls in diagnosis and management","volume":"3","author":"J Markowitz","year":"1983","journal-title":"Hepatology"},{"issue":"02","key":"ref28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00247-016-3728-2","article-title":"Giant hepatic regenerative nodules in Alagille syndrome","volume":"47","author":"J B Rapp","year":"2017","journal-title":"Pediatr Radiol"},{"issue":"02","key":"ref29","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/MPG.0000000000000945","article-title":"Solitary hepatic nodule adjacent to the right portal vein: a common finding of Alagille syndrome?","volume":"62","author":"A Alhammad","year":"2016","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"05","key":"ref30","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/01.mpg.0000179759.60048.c4","article-title":"Hepatocellular carcinoma in children with Alagille syndrome","volume":"41","author":"V A Bhadri","year":"2005","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ijscr.2016.03.032","article-title":"Focal liver hyperplasia in a patient with Alagille syndrome: diagnostic difficulties. A case report","volume":"25","author":"R Ennaifer","year":"2016","journal-title":"Int J Surg Case Rep"},{"issue":"963","key":"ref32","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1259\/bjr\/63424939","article-title":"Regenerating nodules in arteriohepatic syndrome: a case report","volume":"81","author":"M A Syed","year":"2008","journal-title":"Br J Radiol"},{"issue":"10","key":"ref33","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1007\/s00247-010-1784-6","article-title":"Hepatocellular carcinoma and regenerating nodule in a 3-year-old child with Alagille syndrome","volume":"40","author":"S C Wetli","year":"2010","journal-title":"Pediatr Radiol"},{"issue":"01","key":"ref34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.prp.2004.11.007","article-title":"Hepatocellular carcinoma occurring in Alagille syndrome","volume":"201","author":"B Kim","year":"2005","journal-title":"Pathol Res 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Gastroenterol"},{"issue":"11","key":"ref38","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1007\/s10620-009-1123-7","article-title":"Management of large hepatocellular carcinoma in adult patients with Alagille syndrome: a case report and review of literature","volume":"55","author":"S Tsai","year":"2010","journal-title":"Dig Dis Sci"},{"issue":"01","key":"ref39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/ol.2016.4609","article-title":"Oncogenic role of the Notch pathway in primary liver cancer","volume":"12","author":"J Lu","year":"2016","journal-title":"Oncol Lett"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: the catalogue of somatic mutations in cancer","volume":"47","author":"J G Tate","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"05","key":"ref41","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.clinre.2013.05.008","article-title":"Notch signalling beyond liver development: emerging concepts in liver repair and oncogenesis","volume":"37","author":"C M Morell","year":"2013","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"20","key":"ref42","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1161\/01.CIR.0000037221.45902.69","article-title":"Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and\/or Alagille syndrome","volume":"106","author":"D B McElhinney","year":"2002","journal-title":"Circulation"},{"issue":"13","key":"ref43","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/hmg\/8.13.2443","article-title":"The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome","volume":"8","author":"K M Loomes","year":"1999","journal-title":"Hum Mol Genet"},{"issue":"06","key":"ref44","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1073\/pnas.0709663105","article-title":"Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development","volume":"105","author":"F A High","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"23","key":"ref45","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1242\/dev.084871","article-title":"Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome","volume":"139","author":"J J Hofmann","year":"2012","journal-title":"Development"},{"issue":"11","key":"ref46","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1161\/01.CIR.0000121361.01862.A4","article-title":"Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality","volume":"109","author":"B M Kamath","year":"2004","journal-title":"Circulation"},{"issue":"01","key":"ref47","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1542\/peds.111.1.167","article-title":"Bleeding tendency in children with Alagille syndrome","volume":"111","author":"P Lykavieris","year":"2003","journal-title":"Pediatrics"},{"issue":"01","key":"ref48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/01.MPG.0000162776.67758.2F","article-title":"Intracranial vascular abnormalities in patients with Alagille syndrome","volume":"41","author":"K M Emerick","year":"2005","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"04","key":"ref49","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/s00247-017-4043-2","article-title":"Spectrum of cerebral arterial and venous abnormalities in Alagille syndrome","volume":"48","author":"C D Carpenter","year":"2018","journal-title":"Pediatr Radiol"},{"issue":"09","key":"ref50","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1136\/jmg.37.9.658","article-title":"JAGGED1 expression in human embryos: correlation with the Alagille syndrome phenotype","volume":"37","author":"E A Jones","year":"2000","journal-title":"J Med Genet"},{"issue":"01","key":"ref51","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ajmg.a.34369","article-title":"Renal anomalies in Alagille syndrome: a disease-defining feature","volume":"158A","author":"B M Kamath","year":"2012","journal-title":"Am J Med Genet A"},{"issue":"02","key":"ref52","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s00247-001-0599-x","article-title":"Vertebral anomalies in children with Alagille syndrome: an analysis of 50 consecutive patients","volume":"32","author":"E Sanderson","year":"2002","journal-title":"Pediatr Radiol"},{"issue":"02","key":"ref53","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1001\/archotol.1990.01870020093025","article-title":"Temporal bone histopathologic findings in Alagille syndrome","volume":"116","author":"T Okuno","year":"1990","journal-title":"Arch Otolaryngol Head Neck Surg"},{"issue":"01","key":"ref54","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1038\/s41598-017-02574-7","article-title":"Requirement for Jagged1-Notch2 signaling in patterning the bones of the mouse and human middle ear","volume":"7","author":"C S Teng","year":"2017","journal-title":"Sci Rep"},{"issue":"01","key":"ref55","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/00005176-200501000-00014","article-title":"Deficits in size-adjusted bone mass in children with Alagille syndrome","volume":"40","author":"I E Olsen","year":"2005","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"01","key":"ref56","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/MPG.0b013e3181cb9629","article-title":"Pathologic lower extremity fractures in children with Alagille syndrome","volume":"51","author":"C B Bales","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bone.2016.07.006","article-title":"Jagged1 expression by osteoblast-lineage cells regulates trabecular bone mass and periosteal expansion in mice","volume":"91","author":"D W Youngstrom","year":"2016","journal-title":"Bone"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"115576","DOI":"10.1016\/j.bone.2020.115576","article-title":"Bone geometry and microarchitecture deficits in children with Alagille syndrome","volume":"141","author":"J M Kindler","year":"2020","journal-title":"Bone"},{"issue":"02","key":"ref59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/ajmg.10579","article-title":"Facial features in Alagille syndrome: specific or cholestasis facies?","volume":"112","author":"B M Kamath","year":"2002","journal-title":"Am J Med Genet"},{"key":"ref60","volume-title":"Alagille syndrome","author":"M Mouzami","year":"2018"},{"issue":"06","key":"ref61","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1093\/hmg\/ddr575","article-title":"Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype of Alagille syndrome patients","volume":"21","author":"R Humphreys","year":"2012","journal-title":"Hum Mol Genet"},{"issue":"04","key":"ref62","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/sj.eye.6701508","article-title":"The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic","volume":"19","author":"C A Rennie","year":"2005","journal-title":"Eye (Lond)"},{"issue":"01","key":"ref63","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0161-6420(97)30358-3","article-title":"Ocular ultrasound in Alagille syndrome: a new sign","volume":"104","author":"K K Nischal","year":"1997","journal-title":"Ophthalmology"},{"issue":"02","key":"ref64","first-page":"330","article-title":"Ocular abnormalities in Alagille syndrome","volume":"106","author":"M Hingorani","year":"1999","journal-title":"Ophthalmology"},{"issue":"04","key":"ref65","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/00005176-200210000-00007","article-title":"Rethinking growth failure in Alagille syndrome: the role of dietary intake and steatorrhea","volume":"35","author":"A J Rovner","year":"2002","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"02","key":"ref66","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/ajcn\/52.2.203","article-title":"Anthropometric evaluation of children with chronic liver disease","volume":"52","author":"R J Sokol","year":"1990","journal-title":"Am J Clin Nutr"},{"issue":"02","key":"ref67","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0022-3476(99)70411-7","article-title":"Growth, nutritional status, body composition, and energy expenditure in prepubertal children with Alagille syndrome","volume":"134","author":"D Wasserman","year":"1999","journal-title":"J Pediatr"},{"issue":"06","key":"ref68","first-page":"1477","article-title":"Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature","volume":"76","author":"J C Bucuvalas","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"issue":"04","key":"ref69","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1053\/j.gastro.2017.11.002","article-title":"Mouse model of Alagille syndrome and mechanisms of Jagged1 missense mutations","volume":"154","author":"E R Andersson","year":"2018","journal-title":"Gastroenterology"},{"issue":"06","key":"ref70","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1097\/MPG.0b013e3181ef3771","article-title":"Health status of patients with Alagille syndrome","volume":"51","author":"S A Elisofon","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"01","key":"ref71","first-page":"647A","article-title":"Neurocognitive status in alagille syndrome: Results of a multi-center prospective observational study","volume":"66","author":"D H Leung","year":"2017","journal-title":"Hepatology"},{"issue":"02","key":"ref72","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.jpeds.2015.04.077","article-title":"Quality of life and its determinants in a multicenter cohort of children with Alagille syndrome","volume":"167","author":"B M Kamath","year":"2015","journal-title":"J Pediatr"},{"issue":"04","key":"ref73","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/hmg\/10.4.405","article-title":"Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome","volume":"10","author":"J D Morrissette","year":"2001","journal-title":"Hum Mol Genet"},{"issue":"04","key":"ref74","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1086\/374386","article-title":"Conditional JAG1 mutation shows the developing heart is more sensitive than developing liver to JAG1 dosage","volume":"72","author":"F Lu","year":"2003","journal-title":"Am J Hum Genet"},{"issue":"21","key":"ref75","doi-asserted-by":"crossref","first-page":"6247","DOI":"10.1111\/j.1742-4658.2009.07333.x","article-title":"The tetralogy of Fallot-associated G274D mutation impairs folding of the second epidermal growth factor repeat in Jagged-1","volume":"276","author":"C Guarnaccia","year":"2009","journal-title":"FEBS 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Vandriel","year":"2020","journal-title":"Hepatology"},{"issue":"06","key":"ref79","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"P D Stenson","year":"2017","journal-title":"Hum Genet"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-3-319-94571-2_3","volume-title":"Genetics of Alagille syndrome","author":"M A Gilbert","year":"2018"},{"issue":"04","key":"ref81","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ajmg.a.36946","article-title":"Exome sequencing reveals compound heterozygous mutations in ATP8B1 in a JAG1\/NOTCH2 mutation-negative patient with clinically diagnosed Alagille syndrome","volume":"167A","author":"C M Grochowski","year":"2015","journal-title":"Am J Med Genet A"},{"issue":"03","key":"ref82","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/ajmg.a.37512","article-title":"Compound heterozygous mutations in NEK8 in siblings with end-stage renal disease with hepatic and cardiac anomalies","volume":"170","author":"R Rajagopalan","year":"2016","journal-title":"Am J Med Genet A"},{"issue":"05","key":"ref83","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/hep4.1149","article-title":"Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset","volume":"2","author":"S B Schatz","year":"2018","journal-title":"Hepatol Commun"},{"issue":"06","key":"ref84","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1136\/jmg.31.6.453","article-title":"Segregation analysis of Alagille syndrome","volume":"31","author":"S Dhorne-Pollet","year":"1994","journal-title":"J Med Genet"},{"issue":"04","key":"ref85","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/jmg.32.4.264","article-title":"Alagille syndrome: family studies","volume":"32","author":"F V Elmslie","year":"1995","journal-title":"J Med Genet"},{"issue":"02","key":"ref86","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ajmg.a.37429","article-title":"Discordant clinical phenotype in monozygotic twins with Alagille syndrome: possible influence of non-genetic factors","volume":"170A","author":"K Izumi","year":"2016","journal-title":"Am J Med Genet A"},{"issue":"02","key":"ref87","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ajmg.10610","article-title":"Monozygotic twins with a severe form of Alagille syndrome and phenotypic discordance","volume":"112","author":"B M Kamath","year":"2002","journal-title":"Am J Med Genet"},{"issue":"06","key":"ref88","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1086\/301875","article-title":"Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families","volume":"62","author":"I D Krantz","year":"1998","journal-title":"Am J Hum Genet"},{"issue":"02","key":"ref89","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/ajmg.1320190215","article-title":"Arteriohepatic dysplasia (Alagille syndrome): extreme variability among affected family members","volume":"19","author":"S A Shulman","year":"1984","journal-title":"Am J Med Genet"},{"issue":"11","key":"ref90","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/hep4.1574","article-title":"Nonfasted liver stiffness correlates with liver disease parameters and portal hypertension in pediatric cholestatic liver disease","volume":"4","author":"B L Shneider","year":"2020","journal-title":"Hepatol Commun"},{"issue":"01","key":"ref91","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/00005176-199801000-00009","article-title":"Effect of ursodeoxycholic acid therapy on hepatic 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