Gilbert Melissa A, Loomes Kathleen M
Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Transl Gastroenterol Hepatol. 2021 Apr 5;6:22. doi: 10.21037/tgh-2020-03. eCollection 2021.
The observation of bile duct paucity is an important diagnostic finding in children, occurring in roughly 11% of pediatric liver biopsies. Alagille syndrome (ALGS) is a well-defined syndromic form of intrahepatic bile duct paucity that is accompanied by a number of other key features, including cardiac, facial, ocular, and vertebral abnormalities. In the absence of these additional clinical characteristics, intrahepatic bile duct paucity results in a broad differential diagnosis that requires supplementary testing and characterization. Nearly 30 years after ALGS was first described, genetic studies identified a causative gene, , which spearheaded over two decades of research aimed to meticulously delineate the molecular underpinnings of ALGS. These advancements have characterized ALGS as a genetic disease and led to testing strategies that offer the ability to detect a pathogenic genetic variant in almost 97% of individuals with ALGS. Having a molecular understanding of ALGS has allowed for the development of numerous and disease models, which have provided hope and promise for the future generation of gene-based and protein-based therapies. Generation of these disease models has offered scientists a mechanism to study the dynamics of bile duct development and regeneration, and in doing so, produced tools that are applicable to the understanding of other congenital and acquired liver diseases.
胆管稀少的观察是儿童重要的诊断发现，约11%的儿科肝脏活检中会出现。阿拉吉列综合征（ALGS）是一种明确的肝内胆管稀少的综合征形式，伴有许多其他关键特征，包括心脏、面部、眼部和脊柱异常。在没有这些额外临床特征的情况下，肝内胆管稀少会导致广泛的鉴别诊断，需要进行补充检测和特征描述。在首次描述ALGS近30年后，基因研究确定了一个致病基因，这引发了二十多年的研究，旨在精心描绘ALGS的分子基础。这些进展将ALGS定性为一种遗传疾病，并导致了检测策略的出现，几乎能在97%的ALGS患者中检测到致病基因变异。对ALGS的分子理解使得能够开发出众多疾病模型，为未来基于基因和蛋白质的治疗带来了希望。这些疾病模型的产生为科学家提供了一种研究胆管发育和再生动态的机制，并且在此过程中产生了适用于理解其他先天性和获得性肝病的工具。
