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BMC Pediatrics

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Open Access 01-12-2014 | Case report

Crigler-Najjar syndrome type II in a Chinese boy resulting from three mutations in the bilirubin uridine 5′-diphosphate-glucuronosyltransferase (UGT1A1) gene and a family genetic analysis

Authors: Bixia Zheng, Guorui Hu, Jin Yu, Zhifeng Liu

Published in: BMC Pediatrics | Issue 1/2014

Abstract

Background

The UGT1A1 gene encodes a responsible enzyme, UDP-glucuronosyltransferase1A1 (UGT1A1), for bilirubin metabolism. Many mutations have already been identified in patients with inherited disorders with unconjugated hyperbilirubinemia, such as Crigler-Najjar syndromes and Gilbert’s syndrome.

Case presentation

In this report, we presented a boy with intermittent unconjugated hyperbilirubinemia, whose genetic analysis showed a new compound heterozygote determined by three mutations, c.211G > A (p.G71R), c.508_510delTTC (p.F170-) and c.1456 T > G (p.Y486D) in the hotspot regions of the UGT1A1 gene (exons 1 and 5) in Asian populations, presenting a genotype compatible with clinical picture of CNS-II. The family genetic analysis confirmed the origin of these mutations.

Conclusion

UGT1A1 gene analysis should be performed in all cases with unexplained unconjugated hyperbilirubinemia. The description of patients with peculiar genotypes especially including family analysis could help explain the relationship between the genotype and phenotype,it is helpful for clinicians to predict the outcome of the patients.

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Canu G, Minucci A, Zuppi C, Capoluongo E: Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood Cells Mol Dis. 2013, 50 (4): 273-280. 10.1016/j.bcmd.2013.01.003.CrossRefPubMed

Strassburg CP: Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). Best Pract Res Clin Gastroenterol. 2010, 24 (5): 555-571. 10.1016/j.bpg.2010.07.007.CrossRefPubMed

Skierka JM, Kotzer KE, Lagerstedt SA, O’Kane DJ, Baudhuin LM: UGT1A1 genetic analysis as a diagnostic aid for individuals with unconjugated hyperbilirubinemia. J Pediatr. 2013, 162 (6): 1146-1152. 10.1016/j.jpeds.2012.11.042. 1152 e1141-1142CrossRefPubMed

Sampietro M, Iolascon A: Molecular pathology of Crigler-Najjar type I and II and Gilbert’s syndromes. Haematologica. 1999, 84 (2): 150-157.PubMed

Ghosh SS, Lu Y, Lee SW, Wang X, Guha C, Roy-Chowdhury J, Roy-Chowdhury N: Role of cysteine residues in the function of human UDP glucuronosyltransferase isoform 1A1 (UGT1A1). Biochem Med. 2005, 392 (Pt 3): 685-692.

Owens IS, Basu NK, Banerjee R: UDP-glucuronosyltransferases: gene structures of UGT1 and UGT2 families. Methods Enzymol. 2005, 400: 1-22.CrossRefPubMed

Sugatani J: Function, genetic polymorphism, and transcriptional regulation of human UDP-glucuronosyltransferase (UGT) 1A1. Drug Metab Pharmacokinet. 2013, 28 (2): 83-92. 10.2133/dmpk.DMPK-12-RV-096.CrossRefPubMed

Huang CS, Chang PF, Huang MJ, Chen ES, Hung KL, Tsou KI: Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia. Pediatr Res. 2002, 52 (4): 601-605. 10.1203/00006450-200210000-00022.CrossRefPubMed

Huang CS, Chang PF, Huang MJ, Chen ES, Chen WC: Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia. Gastroenterology. 2002, 123 (1): 127-133. 10.1053/gast.2002.34173.CrossRefPubMed

10.

Yamamoto K, Sato H, Fujiyama Y, Doida Y, Bamba T: Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert’s syndrome and Crigler-Najjar syndrome type II. Biochim Biophys Acta. 1998, 1406 (3): 267-273. 10.1016/S0925-4439(98)00013-1.CrossRefPubMed

11.

Wu JX, Cheng GY, Huang J: A homozygous mutation in a Chinese man with Crigler-Najjar syndrome type II and a family genetic analysis. J Dig Dis. 2008, 9 (2): 89-94. 10.1111/j.1751-2980.2008.00328.x.CrossRefPubMed

12.

Minucci A, Canu G, Gentile L, Cimino V, Giardina B, Zuppi C, Capoluongo E: Identification of a novel mutation in UDP-glucuronosyltransferase (UGT1A1) gene in a child with neonatal unconjugated hyperbilirubinemia. Clin Biochem. 2013, 46 (1–2): 170-172.CrossRefPubMed

13.

Sneitz N, Bakker CT, de Knegt RJ, Halley DJ, Finel M, Bosma PJ: Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants. Hum Mutat. 2010, 31 (1): 52-59. 10.1002/humu.21133.CrossRefPubMed

14.

Maruo Y, Ozgenc F, Mimura Y, Ota Y, Matsui K, Takahashi H, Mori A, Taga T, Takano T, Sato H, Takeuchi H: Compound heterozygote of a novel missense mutation (p.K402T) and a double missense mutation (p.[G71R;Y486D]) in type II Crigler-Najjar syndrome. J Pediatr Gastroenterol Nutr. 2011, 52 (3): 362-365. 10.1097/MPG.0b013e3181fcafb8.CrossRefPubMed

15.

Petit F, Gajdos V, Capel L, Parisot F, Myara A, Francoual J, Labrune P: Crigler-Najjar type II syndrome may result from several types and combinations of mutations in the UGT1A1 gene. Clin Genet. 2006, 69 (6): 525-527. 10.1111/j.1399-0004.2006.00616.x.CrossRefPubMed

16.

Ritter JK, Yeatman MT, Kaiser C, Gridelli B, Owens IS: A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase. J Biol Chem. 1993, 268 (31): 23573-23579.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/267/prepub

Title: Crigler-Najjar syndrome type II in a Chinese boy resulting from three mutations in the bilirubin uridine 5′-diphosphate-glucuronosyltransferase (UGT1A1) gene and a family genetic analysis
Authors: Bixia Zheng
Guorui Hu
Jin Yu
Zhifeng Liu
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Pediatrics / Issue 1/2014
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/1471-2431-14-267

At a glance: The STEP trials

Springer Medicine

Crigler-Najjar syndrome type II in a Chinese boy resulting from three mutations in the bilirubin uridine 5′-diphosphate-glucuronosyltransferase (UGT1A1) gene and a family genetic analysis

Abstract

Background

Case presentation

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Case presentation

Conclusion

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