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| A case of Gilbert syndrome caused by UGT1A1 gene compound heterozygous mutations |
OU Weijie( ),LIN Su,WU Yilong,ZHU Yueyong*() |
| Liver Research Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China |
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Abstract A case of Gilbert syndrome (GS) with a heterozygous mutation in the UGT1A1 gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. UGT1A1*28 and c.211G>A heterozygous mutations in UGT1A1 gene were found, which may be another type of mutation causing GS in Chinese population.
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Received: 14 October 2019
Published: 16 April 2020
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Corresponding Authors:
ZHU Yueyong
E-mail: ouweijie@fjmu.edu.cn;zhuyueyong@fjmu.edu.cn
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UGT1A1基因复合杂合突变致吉尔伯特综合征一例
一例吉尔伯特综合征患儿自幼反复出现巩膜黄染，无其他自觉症状；血清胆红素水平升高，以非结合胆红素为主；排除胆道梗阻、溶血等其他引起黄疸的因素；基因检测发现患儿尿苷二磷酸葡糖苷酸转移酶1A1（UGT1A1）基因存在UGT1A1*28和c.211G>A杂合突变。
关键词：
吉尔伯特病,
尿苷二磷酸,
葡萄糖醛酸基转移酶,
基因,
突变,
病例报告
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| [1] |
FRETZAYAS A , MOUSTAKI M , LIAPI O et al. Gilbert syndrome[J]. Eur J Pediatr, 2012, 171 (1): 11- 15
doi: 10.1007/s00431-011-1641-0
|
|
|
| [2] |
HIRSCHFIELD G M , ALEXANDER G J . Gilbert's syndrome:an overview for clinical biochemists[J]. Ann Clin Biochem, 2006, 43 (Pt 5): 340- 343
doi: 10.1258/000456306778520034
|
|
|
| [3] |
KAMAL S , ABDELHAKAM S , GHORABA D et al. The frequency, clinical course, and health related quality of life in adults with Gilbert's syndrome:a longitudinal study[J]. BMC Gastroenterol, 2019, 19 (1): 22
doi: 10.1186/s12876-019-0931-2
|
|
|
| [4] |
KADAKOL A , GHOSH S S , SAPPAL B S et al. Genetic lesions of bilirubin uridine-diphospho-glucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes:correlation of genotype to phenotype[J]. Hum Mutat, 2000, 16 (4): 297- 306
doi: 10.1002/1098-1004(200010)16:4<297:AID-HUMU2>3.0.CO;2-Z
|
|
|
| [5] |
SAPPAL B S , GHOSH S S , SHNEIDER B et al. A novel intronic mutation results in the use of a cryptic splice acceptor site within the coding region of UGT1A1, causing Crigler-Najjar syndrome type 1[J]. Mol Genet Metab, 2002, 75 (2): 134- 142
doi: 10.1006/mgme.2001.3284
|
|
|
| [6] |
WAGNER K H , SHIELS R G , LANG C A et al. Diagnostic criteria and contributors to Gilbert's syndrome[J]. Crit Rev Clin Lab Sci, 2018, 55 (2): 129- 139
doi: 10.1080/10408363.2018.1428526
|
|
|
| [7] |
CANU G , MINUCCI A , ZUPPI C et al. Gilbert and Crigler Najjar syndromes:an update of the UDP-glucuronosyltransferase 1A1(UGT1A1) gene mutation database[J]. Blood Cells Mol Dis, 2013, 50 (4): 273- 280
doi: 10.1016/j.bcmd.2013.01.003
|
|
|
| [8] |
BEUTLER E , GELBART T , DEMINA A . Racial variability in the UDP-glucuronosyltransferase 1(UGT1A1) promoter:a balanced polymorphism for regulation of bilirubin metabolism?[J]. Proc Natl Acad Sci U S A, 1998, 95 (14): 8170- 8174
doi: 10.1073/pnas.95.14.8170
|
|
|
| [9] |
KANAI M , KIJIMA K , SHIRAHATA E et al. Neonatal hyperbilirubinemia and the bilirubin uridine diphosphate-glucuronosyltransferase gene:the common -3263T > G mutation of phenobarbital response enhancer module is not associated with the neonatal hyperbilirubinemia in Japanese[J]. Pediatr Int, 2005, 47 (2): 137- 141
doi: 10.1111/j.1442-200x.2005.02030.x
|
|
|
| [10] |
YANG H , WANG Q , ZHENG L et al. Clinical significance of UGT1A1 genetic analysis in Chinese neonates with severe hyperbilirubinemia[J]. Pediatr Neonatol, 2016, 57 (4): 310- 317
doi: 10.1016/j.pedneo.2015.08.008
|
|
|
| [11] |
YU Z , ZHU K , WANG L et al. Association of neonatal hyperbilirubinemia with UGT1A1 gene polymorphisms:a meta-analysis[J]. Med Sci Monit, 2015, 21 3104- 3114
doi: 10.12659/msm.894043
|
|
|
| [12] |
MARUO Y , NAKAHARA S , YANAGI T et al. Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type Ⅱ and Gilbert syndrome[J]. J Gastroenterol Hepatol, 2016, 31 (2): 403- 408
doi: 10.1111/jgh.13071
|
|
|
| [13] |
KALOTYCHOU V , KARAKOSTA M , TZANETEA R et al. Contribution of G71R mutation to Gilbert's syndrome phenotype in a Greek patient:A case report[J]. World J Gastrointest Pharmacol Ther, 2011, 2 (5): 42- 45
doi: 10.4292/wjgpt.v2.i5.42
|
|
|
| [14] |
LI Y , BUCKLEY D , WANG S et al. Genetic polymorphisms in the TATA box and upstream phenobarbital-responsive enhancer module of the UGT1A1 promoter have combined effects on UDP-glucuronosyltransferase 1A1 transcription mediated by constitutive androstane receptor, pregnane X receptor, or glucocorticoid receptor in human liver[J]. Drug Metab Dispos, 2009, 37 (9): 1978- 1986
doi: 10.1124/dmd.109.027409
|
|
|
| [15] |
KADAKOL A , GHOSH S S , SAPPAL B S et al. Genetic lesions of bilirubin uridine-diphospho-glucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes:correlation of genotype to phenotype[J]. Hum Mutat, 2000, 16 (4): 297- 306
doi: 10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z
|
|
|
| [16] |
ABUDUXIKUER K, FANG L J, LI L T, et al. UGT1A1 genotypes and unconjugated hyperbilirubine-mia phenotypes in post-neonatal Chinese children: A retrospective analysis and quantitative correlation[J/OL]. Medicine (Baltimore), 2018, 97(49): e13576. DOI: 10.1097/MD.0000000000013576.
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