title: Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients.
abstract: Alagille syndrome (AGS) is an autosomal dominant disorder caused by mutations in Jagged1 (JAG1), a ligand in the evolutionarily conserved Notch signaling pathway. Previous studies have demonstrated that a wide spectrum of JAG1 mutations result in AGS. These include total gene deletions, protein truncating, splicing and missense mutations which are distributed across the coding region of the gene. Here we present results of JAG1 mutation screening by SSCP and FISH in 105 patients with AGS. For these studies, new primers were designed for 12 exons. Mutations were identified in 63/105 patients (60%). The spectrum of the JAG1 mutations presented here is consistent with previously reported results. Eighty three percent (52/63) of the mutations were protein truncating, 11% (7/63) were missense, 2% (1/63) were splice site, and 5% (3/63) were total gene deletions demonstrable by FISH. Six of the missense mutations are novel. As has been reported previously, there is no apparent relationship between genotype and clinical phenotype.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Colliton
authors.forename: L
authors.initials: L
authors.lastname: Bason
authors.forename: F M
authors.initials: FM
authors.lastname: Lu
authors.forename: D A
authors.initials: DA
authors.lastname: Piccoli
authors.forename: I D
authors.initials: ID
authors.lastname: Krantz
authors.forename: N B
authors.initials: NB
authors.lastname: Spinner
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins; D004247:DNA