JAG1
阿拉吉尔综合征
外显率
Notch信号通路
表型
生物信息学
生物
疾病
医学
胆汁酸
肝病
遗传学
内科学
病理
胆汁淤积
基因
作者
Taisa Kohut,Melissa A. Gilbert,Kathleen M. Loomes
出处
期刊:Seminars in Liver Disease
[Georg Thieme Verlag KG]
日期:2021-07-02
卷期号:41 (04): 525-537
被引量:26
标识
DOI:10.1055/s-0041-1730951
摘要
Alagille syndrome (ALGS) is an autosomal dominant disorder caused by pathogenic variants in JAG1 or NOTCH2, which encode fundamental components of the Notch signaling pathway. Clinical features span multiple organ systems including hepatic, cardiac, vascular, renal, skeletal, craniofacial, and ocular, and occur with variable phenotypic penetrance. Genotype-phenotype correlation studies have not yet shown associations between mutation type and clinical manifestations or severity, and it has been hypothesized that modifier genes may modulate the effects of JAG1 and NOTCH2 pathogenic variants. Medical management is supportive, focusing on clinical manifestations of disease, with liver transplant indicated for severe pruritus, liver synthetic dysfunction, portal hypertension, bone fractures, and/or growth failure. New therapeutic approaches are under investigation, including ileal bile acid transporter (IBAT) inhibitors and other approaches that may involve targeted interventions to augment the Notch signaling pathway in involved tissues.
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