Abstract
The Alagille syndrome is a multisystem developmental disease caused by mutations in Notch signaling pathway genes; typically JAG1 and very rarely NOTCH2. The syndrome is characterized by a wide variety of affected organs, including liver, heart, kidney, eye, spine, vasculature, and face. Within each organ, there are a range of abnormalities sometimes ranging from trivial to fatal. The most severe end of the spectrum of liver disease in Alagille syndrome is marked by profound cholestasis, with intense pruritus, hypercholesterolemia, xanthomas, jaundice, and fat malabsorption. Liver transplantation is successful at treating and curing the liver disease, but other systemic manifestations persist or progress. The identification of JAG1 as the cause in over 90 % and NOTCH2 in approximately 1 % has led to tremendous advances in understanding the pathogenesis of ALGS and also normal development. Analysis of mutation carriers has greatly expanded the number and the spectrum of Alagille syndrome patients and provided useful precision for family planning.
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Abbreviations
- JAG1 :
-
Italicized gene
- Notch:
-
Signaling pathway
- Notch:
-
Receptor
- NOTCH2, NOTCH3 :
-
Italicized gene
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Kamath, B.M., Piccoli, D.A. (2014). Alagille Syndrome. In: Murray, K., Horslen, S. (eds) Diseases of the Liver in Children. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9005-0_11
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