Van gen naar ziekte; arteriohepatische dysplasie - Het syndroom van Alagille

Alagille syndrome (AGS), also known as arteriohepatic dysplasia, is an autosomal dominant disorder with a prevalence of approximately one in 70,000 live births. AGS is characterised by intrahepatic bile duct paucity and other developmental abnormalities affecting the heart, liver, eyes, vertebrae and the craniofacial region. Mutations in the JAGI gene have been demonstrated to cause Alagille syndrome. JAGI encodes a cellular membrane-bound ligand for the Notch receptor and is expressed during the normal development of tissues affected in Alagille syndrome. JAGI mutations are detected in approximately 70% of AGS patients and are mostly protein truncating mutations. JAGI mutations have also been described in patients that do not demonstrate the complete AGS phenotype, suggesting that the phenotypic spectrum of JAGI mutations is broader than thus far assumed.