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Alagille Syndrome: Overview and Introduction

  • David A. PiccoliEmail author
Chapter

Abstract

The manifestations of Alagille syndrome include the most complex and most interesting of all pediatric liver diseases. The hepatic disease of ALGS ranges from inconsequential to failure, and the manifestations in many other organs also vary from trivial to catastrophic. The dominant mode of inheritance and the common occurrence of de novo mutations have led to fascinating genetic discoveries, and the presence of a normal gene in all affected individuals may lead to novel genetic therapies based on regulation of gene expression. The ALGS is the most extensively studied of any single gene defect that is involved in human embryogenesis. Notch signaling is an important mechanism for cell to cell communication, having developed early on in evolution, and it is highly conserved in all species studied. While much has been learned about the Alagille syndrome over the 50 years since its first description, there are many current clinical challenges and opportunities for the development of novel and effective therapies. In the subsequent chapters of this book, the extensive compilation of the knowledge about Alagille syndrome and Notch signaling will serve as a framework for investigation and discovery into the mechanisms and therapies of this extremely important and fascinating disease.

Keywords

Cholestasis Bile duct paucity JAGGED1 NOTCH2 Notch signaling pathway Pruritus 

Suggested Reading

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    Alagille D, Odievre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental and sexual development, and cardiac murmur. J Pediatr. 1975;86(1):63–71.CrossRefGoogle Scholar
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    Li L, Krantz ID, Deng Y, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997;16(3):243–51.CrossRefGoogle Scholar
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    Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, Piccoli DA, Meltzer PS, Spinner NB, Collins FS, Chandrasekharappa SC. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16(3):235–42. PMID: 9207787.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology and NutritionUniversity of Pennsylvania Perelman School of Medicine, The Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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