Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome.
Gilbert syndrome is a mild hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). The mutation, A(TA)7TAA, is thought to be the sole cause of the syndrome in Caucasians, but an enhancer polymorphism (T-3279G) that lowers transcriptional activity has recently been reported. We have tested the linkage of the two mutations in 11 Caucasians and 12 Japanese patients who were homozygous for A(TA)7TAA. All 23 patients were also homozygous for T-3279G, indicating that T-3279G and A(TA)7TAA were linked. The decrease in transcription caused by both mutations together may be essential to the syndrome.
Maruo
Yoshihiro
Y
Department of Pediatrics, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, 520-2192, Japan. maruo@belle.shiga-med.ac.jp
D'Addario
Carlos
C
Mori
Asami
A
Iwai
Masaru
M
Takahashi
Hiroko
H
Sato
Hiroshi
H
Takeuchi
Yoshihiro
Y
D044466:Asian People; D005878:Gilbert Disease / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D013577:Syndrome; D014158:Transcription, Genetic; D044465:White People; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme