alagille syndrome

Summary

Summary: A multisystem disorder that is characterized by aplasia of intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC), and malformations in the cardiovascular system, the eyes, the vertebral column, and the facies. Major clinical features include JAUNDICE, and congenital heart disease with peripheral PULMONARY STENOSIS. Alagille syndrome may result from heterogeneous gene mutations, including mutations in JAG1 on CHROMOSOME 20 (Type 1) and NOTCH2 on CHROMOSOME 1 (Type 2).

Top Publications

  1. Guadagni M, Cocchi S, Tagariello T, Piana G. Case report: Alagille syndrome. Minerva Stomatol. 2005;54:593-600 pubmed
    The clinical case of a boy aged 6 years suffering from Alagille syndrome is described...
  2. Elisofon S, Emerick K, Sinacore J, Alonso E. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51:759-65 pubmed publisher
    The aim of the study was to assess health-related quality of life (HRQOL) in children with Alagille syndrome (AGS) in comparison with a normative population and other chronic diseases, and also to examine the effect of AGS-specific ..
  3. Crosnier C, Driancourt C, Raynaud N, Hadchouel M, Meunier Rotival M. Fifteen novel mutations in the JAGGED1 gene of patients with Alagille syndrome. Hum Mutat. 2001;17:72-3 pubmed
    Mutations in the human JAGGED1 gene cause Alagille syndrome, an autosomal dominant developmental disorder. The gene encodes a transmembrane protein which is a ligand of Notch receptors...
  4. Spinner N, Colliton R, Crosnier C, Krantz I, Hadchouel M, Meunier Rotival M. Jagged1 mutations in alagille syndrome. Hum Mutat. 2001;17:18-33 pubmed
    We have summarized data on 233 Alagille syndrome patients reported with mutations in Jagged1 (JAG1). This data has been published by seven different laboratories in Europe, the United States, Australia, and Japan...
  5. Kamath B, Spinner N, Emerick K, Chudley A, Booth C, Piccoli D, et al. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109:1354-8 pubmed
    b>Alagille syndrome (AGS) is a dominantly inherited multisystem disorder involving the liver, heart, eyes, face, and skeleton, caused by mutations in Jagged1. Intracranial bleeding is a recognized complication and cause of mortality in AGS...
  6. Crosnier C, Driancourt C, Raynaud N, Dhorne Pollet S, Pollet N, Bernard O, et al. Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome. Gastroenterology. 1999;116:1141-8 pubmed
    Mutations in the JAGGED1 gene are responsible for the Alagille syndrome, an autosomal dominant disorder characterized by neonatal jaundice, intrahepatic cholestasis, and developmental disorders affecting the liver, heart, vertebrae, eyes,..
  7. Byrne J, Meara N, Rayner A, Thompson R, Knisely A. Lack of hepatocellular CD10 along bile canaliculi is physiologic in early childhood and persistent in Alagille syndrome. Lab Invest. 2007;87:1138-48 pubmed
    ..activity (NEA) has been recommended as a marker of cholestasis in adults but not in children with Alagille syndrome (AGS). We investigated ontogenic and disease-related differences in the expression of CD10...
  8. Lykavieris P, Crosnier C, Trichet C, Meunier Rotival M, Hadchouel M. Bleeding tendency in children with Alagille syndrome. Pediatrics. 2003;111:167-70 pubmed
    ..intracranial bleeding is now a widely recognized complication and cause of mortality in patients with Alagille syndrome. The pathogenesis of intracranial bleeding in these patients remains unclear...
  9. Bidaguren A, Blanco A, Gibelalde A, Irigoyen C. [Progressive geographic chorioretinopathy associated with Alagille syndrome]. Arch Soc Esp Oftalmol. 2007;82:513-5 pubmed
    We report the case of a patient with the genetic diagnosis of Alagille Syndrome, who has attended our hospital since 1992, and has shown a progressive bilateral chorioretinopathy with severe deterioration in visual acuity.

More Information

Publications62

  1. Kamath B, Loomes K, Piccoli D. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;50:580-6 pubmed publisher
    b>Alagille syndrome is a highly variable, autosomal dominant disorder that affects the liver, heart, eyes, face, skeleton, kidneys, and vascular system...
  2. Yuan Z, Okaniwa M, Nagata I, Tazawa Y, Ito M, Kawarazaki H, et al. The DSL domain in mutant JAG1 ligand is essential for the severity of the liver defect in Alagille syndrome. Clin Genet. 2001;59:330-7 pubmed
    b>Alagille syndrome (AGS) is a congenital multi-system anomaly mainly characterized by paucity of intrahepatic bile ducts caused by haploinsufficiency of the Jagged 1 gene (JAG1)...
  3. Kamath B, Stolle C, Bason L, Colliton R, Piccoli D, Spinner N, et al. Craniosynostosis in Alagille syndrome. Am J Med Genet. 2002;112:176-80 pubmed
    b>Alagille syndrome is a multisystem developmental disorder with primary involvement of the liver, heart, skeleton, eyes and facial structures, and demonstrates highly variable expressivity with respect to all of the involved systems...
  4. Emerick K, Whitington P. Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome. Hepatology. 2002;35:1501-6 pubmed
    b>Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol...
  5. Sokol R. Re: Article by Kamath et al.-"Facial features in Alagille Syndrome". Am J Med Genet A. 2004;124A:220-1; reply 222-3 pubmed
  6. Boyer Di Ponio J, Wright Crosnier C, Groyer Picard M, Driancourt C, Beau I, Hadchouel M, et al. Biological function of mutant forms of JAGGED1 proteins in Alagille syndrome: inhibitory effect on Notch signaling. Hum Mol Genet. 2007;16:2683-92 pubmed
    Heterozygous mutations in JAGGED1, encoding a single-pass transmembrane ligand for the Notch receptors, cause Alagille syndrome (AGS), a polymalformative disorder affecting the liver, heart, eyes and skeleton and characterized by a ..
  7. Röpke A, Kujat A, Gräber M, Giannakudis J, Hansmann I. Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille syndrome. Hum Mutat. 2003;21:100 pubmed
    b>Alagille syndrome (AGS) is an autosomal dominant disorder characterized by five major symptoms: cholestasis, vertebral deformity, heart malformations, ocular defects and peculiar facial appearance...
  8. McElhinney D, Krantz I, Bason L, Piccoli D, Emerick K, Spinner N, et al. Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome. Circulation. 2002;106:2567-74 pubmed
    Cardiovascular anomalies are among the most common features of Alagille syndrome (AGS). Mutations of JAG1 are found in most individuals with AGS...
  9. Li L, Krantz I, Deng Y, Genin A, Banta A, Collins C, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997;16:243-51 pubmed
    b>Alagille syndrome is an autosomal dominant disorder characterized by abnormal development of liver, heart, skeleton, eye, face and, less frequently, kidney...
  10. Wang H, Wang X, Li Q, Chen S, Liu L, Wei Z, et al. Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome. Gene. 2012;499:191-3 pubmed publisher
    b>Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile duct paucity...
  11. Colliton R, Bason L, Lu F, Piccoli D, Krantz I, Spinner N. Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients. Hum Mutat. 2001;17:151-2 pubmed
    b>Alagille syndrome (AGS) is an autosomal dominant disorder caused by mutations in Jagged1 (JAG1), a ligand in the evolutionarily conserved Notch signaling pathway...
  12. Loomes K, Underkoffler L, Morabito J, Gottlieb S, Piccoli D, Spinner N, et al. The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome. Hum Mol Genet. 1999;8:2443-9 pubmed
    ..b>Alagille syndrome (AGS) is an autosomal dominant disorder characterized by developmental abnormalities of the heart, liver, ..
  13. Hofmann J, Briot A, Enciso J, Zovein A, Ren S, Zhang Z, et al. Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome. Development. 2012;139:4449-60 pubmed publisher
    ..the gene encoding the human Notch ligand jagged 1 result in a multisystem autosomal dominant disorder called Alagille syndrome, which includes tetralogy of Fallot among its more severe cardiac pathologies...
  14. Yucel H, Hoorntje S, Bravenboer B. Renal abnormalities in a family with Alagille syndrome. Neth J Med. 2010;68:38-9 pubmed
    b>Alagille syndrome is largely unknown to the general internist because the diagnosis is usually made by a paediatrician...
  15. Vrijens K, Thys S, De Jeu M, Postnov A, Pfister M, Cox L, et al. Ozzy, a Jag1 vestibular mouse mutant, displays characteristics of Alagille syndrome. Neurobiol Dis. 2006;24:28-40 pubmed
    ..Mutations in the human homologue of Jag1 cause Alagille syndrome (AGS), an autosomal dominant disorder associated with liver, heart, eye and skeletal abnormalities, ..
  16. Warthen D, Moore E, Kamath B, Morrissette J, Sanchez Lara P, Sanchez P, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006;27:436-43 pubmed
    b>Alagille syndrome (AGS) is caused by heterozygous mutations in JAG1, and mutations have been previously reported in about 70% of patients who meet clinical diagnostic criteria...
  17. Fabris L, Cadamuro M, Guido M, Spirli C, Fiorotto R, Colledan M, et al. Analysis of liver repair mechanisms in Alagille syndrome and biliary atresia reveals a role for notch signaling. Am J Pathol. 2007;171:641-53 pubmed
    Patients with Alagille syndrome (AGS), a genetic disorder of Notch signaling, suffer from severe ductopenia and cholestasis, but progression to biliary cirrhosis is rare...
  18. Oda T, Elkahloun A, Meltzer P, Chandrasekharappa S. Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene from the Alagille syndrome critical region at 20p12. Genomics. 1997;43:376-9 pubmed
    ..have isolated the human homolog of the rat Jagged1 gene, JAG1, from a CpG island in a YAC clone covering the Alagille syndrome critical region at chromosome 20p12 (tel-SNAP-D20S186-cen)...
  19. Boyer J, Crosnier C, Driancourt C, Raynaud N, Gonzales M, Hadchouel M, et al. Expression of mutant JAGGED1 alleles in patients with Alagille syndrome. Hum Genet. 2005;116:445-53 pubmed
    ..mutations in JAGGED1 (JAG1), encoding a ligand for Notch receptors, have been identified in patients with Alagille syndrome (AGS)...
  20. Oda T, Elkahloun A, Pike B, Okajima K, Krantz I, Genin A, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16:235-42 pubmed
    b>Alagille syndrome (AGS) is an autosomal-dominant disorder characterized by intrahepatic cholestasis and abnormalities of heart, eye and vertebrae, as well as a characteristic facial appearance...
  21. Ryan M, Bales C, Nelson A, Gonzalez D, Underkoffler L, Segalov M, et al. Bile duct proliferation in Jag1/fringe heterozygous mice identifies candidate modifiers of the Alagille syndrome hepatic phenotype. Hepatology. 2008;48:1989-97 pubmed publisher
    b>Alagille syndrome (AGS) is a heterogeneous developmental disorder associated with bile duct paucity and various organ anomalies...
  22. Kamath B, Schwarz K, Hadzic N. Alagille syndrome and liver transplantation. J Pediatr Gastroenterol Nutr. 2010;50:11-5 pubmed publisher
    b>Alagille syndrome is a multisystem disorder in which progressive liver disease with persistent cholestasis and dramatic pruritus often warrant consideration for liver transplantation...
  23. Subramaniam P, Knisely A, Portmann B, Qureshi S, Aclimandos W, Karani J, et al. Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital. J Pediatr Gastroenterol Nutr. 2011;52:84-9 pubmed publisher
    The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis.
  24. Heritage M, MacMillan J, Colliton R, Genin A, Spinner N, Anderson G. Jagged1 (JAG1) mutation detection in an Australian Alagille syndrome population. Hum Mutat. 2000;16:408-16 pubmed
    b>Alagille syndrome (AGS) is an autosomal dominant disorder characterized by abnormal development of the liver, heart, skeleton, eye, and face...
  25. Lykavieris P, Hadchouel M, Chardot C, Bernard O. Outcome of liver disease in children with Alagille syndrome: a study of 163 patients. Gut. 2001;49:431-5 pubmed
    Various opinions have been expressed as to the long term prognosis of liver disease associated with Alagille syndrome (AGS).
  26. Humphreys R, Zheng W, Prince L, Qu X, Brown C, Loomes K, et al. Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype of Alagille syndrome patients. Hum Mol Genet. 2012;21:1374-83 pubmed publisher
    JAGGED1 mutations cause Alagille syndrome, comprising a constellation of clinical findings, including biliary, cardiac and craniofacial anomalies...
  27. Raas Rothschild A, Shteyer E, Lerer I, Nir A, Granot E, Rein A. Jagged1 gene mutation for abdominal coarctation of the aorta in Alagille syndrome. Am J Med Genet. 2002;112:75-8 pubmed
    Congenital cardiac defects such as peripheral pulmonary stenosis are well described in Alagille syndrome (AGS), which is transmitted in an autosomal dominant inheritance...
  28. Bales C, Kamath B, Munoz P, Nguyen A, Piccoli D, Spinner N, et al. Pathologic lower extremity fractures in children with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51:66-70 pubmed publisher
    In this retrospective study, we aimed to determine the incidence and distribution of fractures in patients with Alagille syndrome, 1 of the leading inherited causes of pediatric cholestatic liver disease.
  29. Vajro P, Ferrante L, Paolella G. Alagille syndrome: an overview. Clin Res Hepatol Gastroenterol. 2012;36:275-7 pubmed publisher
    b>Alagille syndrome is an embryofoetopathy, due to mutations in the gene JAG1. It is autosomic dominant with variable expressivity, or sporadic. Neonatal cholestasis is a main feature, due to the paucity of intrahepatic bile ducts...
  30. Lin H, Le Hoang P, Hutchinson A, Chao G, Gerfen J, Loomes K, et al. Alagille syndrome in a Vietnamese cohort: mutation analysis and assessment of facial features. Am J Med Genet A. 2012;158A:1005-13 pubmed publisher
    b>Alagille syndrome (ALGS, OMIM #118450) is an autosomal dominant disorder that affects multiple organ systems including the liver, heart, eyes, vertebrae, and face...
  31. Kamath B, Spinner N, Rosenblum N. Renal involvement and the role of Notch signalling in Alagille syndrome. Nat Rev Nephrol. 2013;9:409-18 pubmed publisher
    b>Alagille syndrome is an autosomal dominant disorder with variable multisystem organ involvement that is caused by mutations in one of two genes in the Notch signalling pathway, JAG1 or NOTCH2...
  32. Modi B, Suh M, Jonas M, Lillehei C, Kim H. Ileal exclusion for refractory symptomatic cholestasis in Alagille syndrome. J Pediatr Surg. 2007;42:800-5 pubmed
    b>Alagille syndrome (AGS) can result in pruritic self-mutilation and disabling or disfiguring xanthomas...
  33. Carlton V, Pawlikowska L, Bull L. Molecular basis of intrahepatic cholestasis. Ann Med. 2004;36:606-17 pubmed
    ..b>Alagille syndrome patients carry mutations in JAG1, and mutations in VPS33B have been identified in patients with ..
  34. Jurkiewicz D, Popowska E, Gläser C, Hansmann I, Krajewska Walasek M. Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients. Hum Mutat. 2005;25:321 pubmed
    b>Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities of the liver, heart, eyes, vertebrae, and face...
  35. Lorent K, Yeo S, Oda T, Chandrasekharappa S, Chitnis A, Matthews R, et al. Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy. Development. 2004;131:5753-66 pubmed
    The Alagille Syndrome (AGS) is a heritable disorder affecting the liver and other organs. Causative dominant mutations in human Jagged 1 have been identified in most AGS patients...
  36. Pilia G, Uda M, Macis D, Frau F, Crisponi L, Balli F, et al. Jagged-1 mutation analysis in Italian Alagille syndrome patients. Hum Mutat. 1999;14:394-400 pubmed
    b>Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region...
  37. Morrissette J, Colliton R, Spinner N. Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome. Hum Mol Genet. 2001;10:405-13 pubmed
    Jagged1 (JAG1) is a cell surface ligand in the Notch signaling pathway and mutations in this gene cause Alagille syndrome (AGS)...
  38. Heritage M, MacMillan J, Anderson G. DHPLC mutation analysis of Jagged1 (JAG1) reveals six novel mutations in Australian alagille syndrome patients. Hum Mutat. 2002;20:481 pubmed
    b>Alagille syndrome (AGS) is an autosomal dominant disorder characterized by abnormal development of the liver, heart, skeleton, eye, and face. Mutations in the Jagged1 gene have been found to result in the AGS phenotype...
  39. McCright B, Lozier J, Gridley T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development. 2002;129:1075-82 pubmed
    b>Alagille syndrome is a human autosomal dominant developmental disorder characterized by liver, heart, eye, skeletal, craniofacial and kidney abnormalities...
  40. Englert C, Grabhorn E, Burdelski M, Ganschow R. Liver transplantation in children with Alagille syndrome: indications and outcome. Pediatr Transplant. 2006;10:154-8 pubmed
    ..Future studies must identify underlying mechanisms of hypercholesterolemia and vascular malformation...
  41. Krantz I, Colliton R, Genin A, Rand E, Li L, Piccoli D, et al. Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. Am J Hum Genet. 1998;62:1361-9 pubmed
    b>Alagille syndrome (AGS) is a dominantly inherited disorder characterized by liver disease in combination with heart, skeletal, ocular, facial, renal, and pancreatic abnormalities...
  42. Kamath B, Bauer R, Loomes K, Chao G, Gerfen J, Hutchinson A, et al. NOTCH2 mutations in Alagille syndrome. J Med Genet. 2012;49:138-44 pubmed publisher
    b>Alagille syndrome (ALGS) is a dominant, multisystem disorder caused by mutations in the Jagged1 (JAG1) ligand in 94% of patients, and in the NOTCH2 receptor in <1%. There are only two NOTCH2 families reported to date...
  43. Stankiewicz P, Rujner J, Loffler C, Kruger A, Nimmakayalu M, Piłacik B, et al. Alagille syndrome associated with a paracentric inversion 20p12.2p13 disrupting the JAG1 gene. Am J Med Genet. 2001;103:166-71 pubmed
    ..JAG1) localized in 20p12 have been recently identified as causal for the anomalies found in patients with Alagille syndrome (AGS)...
  44. Turnpenny P, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2012;20:251-7 pubmed publisher
    b>Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is a multisystem disorder due to defects in components of the Notch signalling pathway, most commonly due to mutation in JAG1 (ALGS type 1), but in a small proportion of ..
  45. Guegan K, Stals K, Day M, Turnpenny P, Ellard S. JAG1 mutations are found in approximately one third of patients presenting with only one or two clinical features of Alagille syndrome. Clin Genet. 2012;82:33-40 pubmed publisher
    b>Alagille syndrome is a multisystem disorder characterized by highly variable expressivity, most frequently caused by heterozygous JAG1 gene mutations...
  46. Krantz I. Alagille syndrome: chipping away at the tip of the iceberg. Am J Med Genet. 2002;112:160-2 pubmed
  47. Yancey P, Asztalos B, Stettler N, Piccoli D, Williams D, Connelly M, et al. SR-BI- and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome. J Lipid Res. 2004;45:1724-32 pubmed
    b>Alagille syndrome is associated with bile duct paucity resulting in liver disease. Patients can be divided into mildly and severely icteric groups, with both groups having altered lipoproteins...
  48. Fischer A, Klamt B, Schumacher N, Glaeser C, Hansmann I, Fenge H, et al. Phenotypic variability in Hey2 -/- mice and absence of HEY2 mutations in patients with congenital heart defects or Alagille syndrome. Mamm Genome. 2004;15:711-6 pubmed
    ..is one of the few Notch target genes, it is also conceivable that HEY2 mutations may account for cases of Alagille syndrome (AGS: variable combinations of heart, skeleton, eye, and facial malformations and cholestasis), in which the ..
  49. Harendza S, Hübner C, Gläser C, Burdelski M, Thaiss F, Hansmann I, et al. Renal failure and hypertension in Alagille syndrome with a novel JAG1 mutation. J Nephrol. 2005;18:312-7 pubmed
    Renal failure and hypertension in Alagille syndrome with a novel JAG1 mutation: Alagille syndrome is an autosomal dominant disorder involving liver, heart, eyes, face, skeleton, and other organs...
  50. Hofmann J, Zovein A, Koh H, Radtke F, Weinmaster G, Iruela Arispe M. Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome. Development. 2010;137:4061-72 pubmed publisher
    Mutations in the human Notch ligand jagged 1 (JAG1) result in a multi-system disorder called Alagille syndrome (AGS)...
  51. Giannakudis J, Röpke A, Kujat A, Krajewska Walasek M, Hughes H, Fryns J, et al. Parental mosaicism of JAG1 mutations in families with Alagille syndrome. Eur J Hum Genet. 2001;9:209-16 pubmed
    The Alagille syndrome (AGS), a congenital disorder affecting liver, heart, skeleton and eye in association with a typical face, is an autosomal dominant disease with nearly complete penetrance and variable expression...
  52. Jones E, Clement Jones M, Wilson D. JAGGED1 expression in human embryos: correlation with the Alagille syndrome phenotype. J Med Genet. 2000;37:658-62 pubmed
    b>Alagille syndrome (AGS, MIM 118450) is an autosomal dominant disorder with a variable phenotype characterised by hepatic, eye, cardiac, and skeletal malformations and a characteristic facial appearance...
  53. Cowan J, Barkhoudarian G, Yang L, Thompson B. Progression of a posterior communicating artery infundibulum into an aneurysm in a patient with Alagille syndrome. Case report. J Neurosurg. 2004;101:694-6 pubmed
    ..in which a posterior communicating artery (PCoA) infundibulum progressed into an aneurysm in a patient with Alagille syndrome (arteriohepatic dysplasia)...