title: NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway.
abstract: Alagille syndrome (AGS) is caused by mutations in the gene for the Notch signaling pathway ligand Jagged1 (JAG1), which are found in 94% of patients. To identify the cause of disease in patients without JAG1 mutations, we screened 11 JAG1 mutation-negative probands with AGS for alterations in the gene for the Notch2 receptor (NOTCH2). We found NOTCH2 mutations segregating in two families and identified five affected individuals. Renal manifestations, a minor feature in AGS, were present in all the affected individuals. This demonstrates that AGS is a heterogeneous disorder and implicates NOTCH2 mutations in human disease.
authors.affiliation: Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McDaniell
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Warthen
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Sanchez-Lara
authors.forename: Athma
authors.initials: A
authors.lastname: Pai
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
authors.forename: David A
authors.initials: DA
authors.lastname: Piccoli
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
mesh_terms: D016738:Alagille Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D051883:Receptor, Notch2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051883:Receptor, Notch2