title: Genetic alterations in the JAG1 gene in Japanese patients with Alagille syndrome.
abstract: Alagille syndrome (AGS) is a congenital anomaly syndrome that affects liver, heart, pulmonary artery, eyes, face, and skeleton. Recently, mutations of the JAG1 gene, which encodes a ligand for the Notch receptor, have been identified in AGS patients. We investigated the JAG1 gene for genetic alterations in eight Japanese AGS patients, using fluorescence in situ hybridization (FISH), single strand conformation polymorphism (SSCP) analysis, and direct sequencing. Subtle genetic alterations were identified in six of the eight patients, including three frameshift mutations, two splice donor mutations, and one nonsense mutation. All alleles with identified mutations can be expected to produce non-functional truncated proteins without a transmembrane domain. There was no apparent correlation between the genotypes of the patients and their affected organs, although the phenotypes of the patients with mutations at the splice donor site were found to be less severe.
authors.affiliation: Human Genome Center, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Onouchi
authors.forename: H
authors.initials: H
authors.lastname: Kurahashi
authors.forename: H
authors.initials: H
authors.lastname: Tajiri
authors.forename: S
authors.initials: S
authors.lastname: Ida
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics*; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D007564:Japan; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; 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