Alagille syndrome involves multiple organ systems, but the primary features include cholestasis evidenced by bile duct paucity on liver biopsy, congenital heart defects typically involving the pulmonary arteries, posterior embryotoxon in the eye, typical facial features, and butterfly vertebrae. Expressivity is variable even within families. This condition is inherited in an autosomal dominant manner. Approximately 30-50% of cases are inherited, while 50-70% are de novo. Most cases of Alagille syndrome are caused by sequence variants of the JAG1 gene followed by deletions/duplications (5-7%). Less than 1% of cases are caused by mutations in the NOTCH2 gene.
This laboratory performs both Sanger sequencing and deletion/duplication by MLPA for the JAG1 gene.