title: Craniosynostosis in Alagille syndrome.
abstract: 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. Alagille syndrome is caused by mutations in the Jagged1 gene. Jagged1 is a ligand in the Notch signaling pathway that has been shown to regulate early cell fate determination. Mutations in Jagged1 have been identified in approximately 80% of patients with Alagille syndrome. We have recently identified two patients with mutation proven Alagille syndrome who also had unilateral coronal craniosynostosis. Both individuals were screened for mutations in fibroblast growth factor receptor 1, 2, 3 and TWIST genes, all associated with various types of craniosynostosis and no mutations were identified. The finding of a conserved form of craniosynostosis in two unrelated patients with Alagille syndrome and mutations in Jagged1 may indicate that Jagged1 plays a role in cranial suture formation.
authors.affiliation: Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Binita M
authors.initials: BM
authors.lastname: Kamath
authors.forename: Catherine
authors.initials: C
authors.lastname: Stolle
authors.forename: Lynn
authors.initials: L
authors.lastname: Bason
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Colliton
authors.forename: David A
authors.initials: DA
authors.lastname: Piccoli
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D016738:Alagille Syndrome / Q000175:diagnosis / Q000473:pathology*; D001652:Bile Ducts / Q000002:abnormalities; D002135:Calcium-Binding Proteins; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011506:Proteins; D017468:Receptors, Fibroblast Growth Factor; D000072099:Serrate-Jagged Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1