title: Fifteen novel mutations in the JAGGED1 gene of patients with Alagille syndrome.
abstract: 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. We report 23 mutations in previously undescribed probands, including 15 novel mutations and 8 recurrent mutations. They map in the part of the gene encoding the extracellular part of the protein. Fifteen mutations are frameshifts and 8 are point mutations. They could give rise to truncated proteins (18/23, including 5 nonsense mutations). There are 2 splice defects, and the 3 missense mutations all cause loss or creation of cysteine residues in the Delta-Serrate-Lag2 domain or in EGF repeats. The inheritance was studied in 14 families, including those of 2 probands previously studied. Two mutations were transmitted from the father and 3 from the mother. Nine mutations were de novo, further confirmation that the majority of cases are sporadic.
authors.affiliation: INSERM Unité 347 affiliée au CNRS, F-94276 Le Kremlin-Bicetre, France.
authors.forename: C
authors.initials: C
authors.lastname: Crosnier
authors.forename: C
authors.initials: C
authors.lastname: Driancourt
authors.forename: N
authors.initials: N
authors.lastname: Raynaud
authors.forename: M
authors.initials: M
authors.lastname: Hadchouel
authors.forename: M
authors.initials: M
authors.lastname: Meunier-Rotival
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D020816:Amino Acid Motifs / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D002135:Calcium-Binding Proteins; D004252:DNA Mutational Analysis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid; 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