The Cardiovascular Manifestations of Alagille Syndrome and JAG1 Mutations

Alagille syndrome is an autosomal-dominant disorder characterized by hepatic, cardiac, ocular, skeletal, and facial abnormalities. The disease gene, Jagged1 (JAG1 ), was identified by molecular analyses of chromosomal alterations involving chromosome 20p. Total gene deletions (3-7%) and intragenic mutations (70%) of JAG1 have been identified in Alagille patients. Identifying JAG1 mutations is challenging, given its size of 26 exons. Methods to identifyboth whole-gene deletions and intragenic mutations of JAG1 are described in detail, including fluorescence in situ hybridization (FISH), conformation-sensitive gel electrophoresis (CSGE), and complementary DNA (cDNA) sequencing.