GILBERTS-SYNDROME IS CAUSED BY A HETEROZYGOUS MISSENSE MUTATION IN THE GENE FOR BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE

Gilbert's syndrome, which is characterized by chronic, non-hemolytic u nconjugated hyperbilirubinemia, is caused by a reduction in the activi ty of hepatic bilirubin UDP-glucuronosyltransferase (UGT). Here, we re port that all examined patients with this disease carried missense mut ations in the gene for UGT and that the mutations were heterozygous, A n expression study in COS cells in vitro, using the expression vector pcDL that carried the mutated gene for UGT from a patient, indicated t hat similar to 14% of the normal UGT activity was expressed, However, the UGT activity of the patient with Gilbert's syndrome was unexpected ly <50% of the normal, perhaps as the result of the dominant negative nature of the mutation.