Alagille Syndrome: Genetics and Functional Models

Overview

Journal Curr Pathobiol Rep

Specialty Pathology

Date 2017 Dec 23

PMID 29270332

Citations 17

Authors

Melissa A Gilbert

Nancy B Spinner

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: We review the genetics of the autosomal dominant, multi-system disorder, Alagille syndrome and provide a summary on how current functional models and emerging biotechnologies are equipped to guide scientists towards novel therapies. The importance of haploinsufficiency as a disease mechanism will be underscored throughout this discussion.

Recent Findings: Alagille syndrome, a human disorder affecting the liver, heart, vasculature, kidney, and other systems, is caused by mutations in the Notch signaling pathway ligand, Jagged1 () or the receptor, . Current advances in animal modeling, cell culture, and human induced pluripotent stem cells, provide new opportunities in which to study disease mechanisms and manifestations.

Summary: We anticipate that the availability of innovative functional models will allow scientists to test new gene therapies or small molecule treatments in physiologically-relevant systems. With these advances, we look forward to the development of new methods to help Alagille syndrome patients.

Citing Articles

The burden of Alagille syndrome: uncovering the potential of emerging therapeutics - a comprehensive systematic literature review.

Bufler P, Howard R, Quadrado L, Lacey G, Terner-Rosenthal J, Goldstein A J Comp Eff Res. 2025; 14(2):e240188.

PMID: 39807752 PMC: 11773862. DOI: 10.57264/cer-2024-0188.

Association of Very Rare Variants with Clinical Features of Alagille Syndrome.

Ferrandino M, Cardiero G, Di Dato F, Cerrato Y, Vitagliano L, Mandato C Genes (Basel). 2024; 15(8).

PMID: 39202394 PMC: 11353882. DOI: 10.3390/genes15081034.

Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome.

Yan J, Huang Y, Cao L, Dong Y, Xu Z, Wang F BMC Pediatr. 2024; 24(1):532.

PMID: 39164659 PMC: 11334458. DOI: 10.1186/s12887-024-04973-y.

Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.

Reis L, Seese S, Costakos D, Semina E Prog Retin Eye Res. 2024; 102:101288.

PMID: 39097141 PMC: 11392650. DOI: 10.1016/j.preteyeres.2024.101288.

Panic at the Bile Duct: How Intrahepatic Cholangiocytes Respond to Stress and Injury.

Hrncir H, Hantelys F, Gracz A Am J Pathol. 2023; 193(10):1440-1454.

PMID: 36870530 PMC: 10548281. DOI: 10.1016/j.ajpath.2023.02.012.

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