Halma Jennifer, Lin Henry C
Division of Gastroenterology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
Division of Pediatric Gastroenterology, Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
Expert Rev Gastroenterol Hepatol. 2023 Jul-Dec;17(9):883-892. doi: 10.1080/17474124.2023.2255518. Epub 2023 Sep 5.
Alagille syndrome (ALGS) is an autosomal dominant, multisystem genetic disorder with wide phenotypic variability caused by mutations in the Notch signaling pathway, specifically from mutations in either the Jagged1 (JAG1) or NOTCH2 gene. The range of clinical features in ALGS can involve various organ systems including the liver, heart, eyes, skeleton, kidney, and vasculature. Despite the genetic mutations being well-defined, there is variable expressivity and individuals with the same mutation may have different clinical phenotypes.
While no clear genotype-phenotype correlation has been identified in ALGS, this review will summarize what is currently known about the genotype-phenotype relationship and how this relationship influences the treatment of the multisystemic disorder. This review includes discussion of numerous studies which have focused on describing the genotype-phenotype relationship of different organ systems in ALGS as well as relevant basic science and population studies of ALGS. A thorough literature search was completed via the PubMed and National Library of Medicine GeneReviews databases including dates from 1969, when ALGS was first identified, to February 2023.
The genetics of ALGS are well defined; however, ongoing investigation to identify genotype-phenotype relationships as well as genetic modifiers as potential therapeutic targets is needed. Clinicians and patients alike would benefit from identification of a correlation to aid in diagnostic evaluation and management.
阿拉吉耶综合征（ALGS）是一种常染色体显性遗传的多系统遗传性疾病，具有广泛的表型变异性，由Notch信号通路中的突变引起，具体是由锯齿状蛋白1（JAG1）或Notch2基因的突变所致。ALGS的临床特征范围可涉及多个器官系统，包括肝脏、心脏、眼睛、骨骼、肾脏和脉管系统。尽管基因突变已明确，但存在可变表达性，具有相同突变的个体可能有不同的临床表型。
虽然在ALGS中尚未确定明确的基因型-表型相关性，但本综述将总结目前已知的基因型-表型关系，以及这种关系如何影响这种多系统疾病的治疗。本综述包括对众多研究的讨论，这些研究专注于描述ALGS中不同器官系统的基因型-表型关系以及ALGS的相关基础科学和人群研究。通过PubMed和美国国立医学图书馆基因评论数据库完成了全面的文献检索，检索日期从1969年（ALGS首次被发现的年份）到2023年2月。
ALGS的遗传学已明确；然而，仍需要持续研究以确定基因型-表型关系以及作为潜在治疗靶点的基因修饰因子。识别相关性将有助于诊断评估和管理，临床医生和患者都将从中受益。
