O. Koiwai et al., GILBERTS-SYNDROME IS CAUSED BY A HETEROZYGOUS MISSENSE MUTATION IN THE GENE FOR BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE, Human molecular genetics, 4(7), 1995, pp. 1183-1186
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.