Alagille Syndrome Clinical Care Program

Alagille Syndrome Research at CHOP

In 1997, we discovered that mutations in Jagged1 cause Alagille syndrome. We were able to do this after narrowing down the location of the Alagille syndrome gene to chromosome 20p12, based on the finding that multiple Alagille syndrome patients had chromosome abnormalities involving this region.

The Jagged1 gene directs the manufacture of a protein found on the surface of some cells. By interacting with proteins on other cell surfaces, the Jagged1 protein helps cells to choose what types of cells they will become (cell fate decisions).

Our current screening methods detect Jagged1 mutations in more than 90% of people with classic clinical Alagille syndrome features. Individuals with Jagged1 mutations have a wide range of clinical findings, ranging from very mild (isolated cardiac murmur or facial features or butterfly vertebrae for example) to very severe (cardiac or liver disease requiring transplantation). We have been studying the full range of clinical features associated with a Jagged1 mutation, and we are working to understand the molecular basis for these differences.

We have recently discovered that a small percentage of patients with Alagille syndrome have mutations in another gene (Notch2) which is known to interact with Jagged1. We are now working to search for Notch2 mutations in additional patients, and determine if there are differences in the clinical presentation associated with Jagged1 and Notch2 mutations. We are also working to define the molecular basis of Notch2 mediated Alagille syndrome.

Currently, our research is focused on:

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