NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway by McDaniell Ryan, Warthen Daniel M, Sanchez-Lara Pedro A, Pai Athma, Krantz Ian D, Piccoli David A, Spinner Nancy B in American journal of human genetics (2006). PubMed

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.

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