Bile Ducts in Regenerative Liver Nodules of Alagille Patients Are Not the Result of Genetic Mosaicism

Alagille syndrome (ALGS) is a complex, multisystem disease associated with mutations in the JAG1 gene. In the liver, ALGS is characterized by paucity of intrahepatic bile ducts. Gene dosage analysis performed on a large, central regenerative nodule with preserved interlobular bile ducts of 2 unrelated ALGS patients, and on surrounding cirrhotic and ductopenic liver parenchyma, showed in both cases complete JAG1 heterozygous deletion in the regenerative nodule and the ductopenic liver, with no differences in gene dosage. Thus, JAG1 mosaicism and differential haploinsufficiency do not explain the presence of bile ducts in centrally located regenerative nodules.