What gene change/mutation causes Alagille syndrome?
There are two genes known to be involved in Alagille syndrome. Changes/mutations in the gene JAG1 cause about 94-96% of Alagille syndrome. The type of changes in the gene can range from "spelling mistakes" to missing or added gene pieces. About 89% of Alagille syndrome is caused by spelling mistakes in JAG1. About 5-7% of Alagille syndrome is caused by big extra or missing pieces of JAG1. Spelling mistakes in the gene NOTCH2 cause about 1-2% of Alagille syndrome. The cause of the remaining 2-5% of Alagille syndrome is not yet known.
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What happens because of the gene changes in JAG1 and NOTCH2?
The job of a gene is to make a protein. Normally, JAG1 makes a protein called Jagged-1 and NOTCH2 makes a protein called Notch 2. These proteins work in the cell to allow for communication between different cells as the baby develops before it is born. This communication is used to build the body properly. Changes in either of these genes causes the proteins to work less or not at all. This probably disrupts the communication between cells and might prevent the body from developing properly. The bile ducts, heart, spine bones, eyes, and face are the main parts of the body affected by the disruption in communication.
- Alagille Syndrome. GeneReviews. https://www.ncbi.nlm.nih.gov/books/NBK1273/
- Alagille Syndrome. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/alagille-syndrome
Does anything make Alagille syndrome worse?
People with Alagille syndrome should avoid contact sports like football, especially if they have chronic liver disease, a large spleen, or problems with their blood vessels. This is because getting hit or injured can cause severe damage to the body. As well, people with liver disease should avoid drinking alcohol because it can cause more liver damage.
Do changes in the JAG1 gene cause any conditions other than Alagille syndrome?
There are not any other conditions that we know of that are caused by genetic changes in JAG1. However, some people with changes in JAG1 don't have all the symptoms of Alagille syndrome, and may not even have enough symptoms to be diagnosed by their doctors with this condition. For example, there have been multiple people reported with JAG1 gene changes who only have heart problems.
Do changes in the NOTCH2 gene cause any conditions other than Alagille syndrome?
There are a few very specific genetic changes in NOTCH2 that cause a condition called Hajdu-Cheney syndrome (also known as serpentine fibula polycystic kidney syndrome). This syndrome causes breakdown of the bones, characteristic facial appearance, cysts (fluid filled sacs) in the kidneys, cleft palate, and heart problems.