Alagille综合征各系统损害的研究进展

Alagille综合征(Alagille syndrome,ALGS)是具有表型特征的慢性胆汁淤积的最常见原因,是一种累及多器官的罕见常染色体显性遗传性疾病.受损器官或部位包括肝脏、心脏、骨骼、眼、面部、肾脏、血管和皮肤.ALGS产生的原因是配体JAG1或受体NOTCH2突变导致Notch信号通路缺陷而引起的机体多个系统和器官损害.肝内胆管缺乏或消失伴临床上五项主要临床特征:[胆汁淤积、心脏缺陷、脊柱畸形(蝴蝶状椎骨)、眼部异常(角膜后胚胎环)和突出的面部特征(倒三角形)]中的三项及其以上就可以进行确诊.近些年,随着分子诊断技术的进步和各系统表型发病原因的不断研究,ALGS越来越受到重视,该文就这两种突变导致的ALGS的临床表现、发病机制和诊断作一综述.

Progress in each system damage of Alagille syndrome

Alagille syndrome (ALGS) is the most common cause of the phenotypic characteristics of chronic cholestasis disease.It is an infrequent multisystem autosomal dominant disorder that developmental abnormalities in several organs including the liver, heart, skeleton, eye and face, kidney, vasculature and skin.Alagille syndrome is caused by mutations in both a ligand(Jagged1 (JAG1)) and receptor(NOTCH2) that activate the Notch signaling pathway.The criteria of Alagille syndrome contains the presentation of 3/5 clinical features including anomalies of the cholestasis, heart defects, spinal deformity (butterfly vertebrae), eye abnormality (posterior embryotoxon) and prominent facial features(inverted triangular face) along with bile duct paucity on liver biopsy.In recent years, with the progress of molecular diagnostic techniques and etiology research for each system phenotype, ALGS has attracted more and more attention.This article reviews the clinical manifestations,pathogenesis and diagnosis of ALGS.