Variations in the JAGGED1 gene have been found to cause Alagille syndrome. Nevertheless, no particular hotspots in the gene have been found; any part of the entire coding regions for JAGGED1 may be involved. Twin sisters with jaundice visited our hospital and were diagnosed with Alagille syndrome. The gene variations in their JAGGED1 coding sequences were evaluated by complementary DNA sequencing. The 12-month-old twin sisters have broad foreheads, deep-set eyes, pointed chins, and triangular faces with jaundice. Clinical testing showed the presence of posterior embryotoxon, butterfly vertebrae, and atrial septal defect. Biochemical indexes showed cholestasis and liver damage. Three conserved variations were identified within exons 22 (c.2612C>G), 24 (c.2957T>A), and 26 (c.3417T>C) in the JAGGED1 coding sequence. The predicted consequences for c.2612C>G, c.2957T>A, and c.3417T>C were p.Pro871Arg, p.Leu986*, and p.Tyr1139=, respectively. The T to A change in the JAGGED1 coding sequence at 2957 will generate a stop codon and might lead to deletion of amino acid 233 at the C terminal of the JAGGED1 protein. Our data suggest that gene variations of c.2612C>G, c.2957T>A, and c.3417T>C, especially c.2957T>A, might have contributed to the pathogenesis of Alagille syndrome in these Chinese twin sisters and provided new gene evidences for Alagille syndrome.
Keywords: Alagille syndrome; JAGGED1; bile duct paucity; butterfly vertebrae; gene variations; posterior embryotoxon.