NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway.
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.
McDaniell
Ryan
R
Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, PA 19104, USA.
Warthen
Daniel M
DM
Sanchez-Lara
Pedro A
PA
Pai
Athma
A
Krantz
Ian D
ID
Piccoli
David A
DA
Spinner
Nancy B
NB
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
D051883:Receptor, Notch2