The cardiovascular manifestations of Alagille syndrome and JAGI mutations

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