Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome
Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome
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DOI：
10.1007/s00439-004-1183-x
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发表时间：
2004-11-01
期刊：
影响因子：
5.3
通讯作者：
Takeuchi, Y
中科院分区：
文献类型：
--
作者：
Maruo, Y;D' Addario, C;Takeuchi, Y
吉尔伯特综合征是一种轻度遗传性非结合型高胆红素血症，由胆红素UDP-葡萄糖醛酸转移酶基因（UGT 1A 1）突变引起。突变，A（TA）7 TAA，被认为是高加索人综合征的唯一原因，但增强子多态性（T-3279 G），降低转录活性最近已被报道。我们在11名白人和12名日本患者中检测了这两种突变的连锁，这些患者均为A（TA）7 TAA纯合子。所有23例患者也都是T-3279 G纯合子，表明T-3279 G和A（TA）7 TAA连锁。由两种突变共同引起的转录减少可能是该综合征的关键。
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.