Crigler-Najjar Syndrome in the Netherlands: Identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants

Human Mutation

Volumn 31, Issue 1, 2010, Pages 52-59

  Sneitz, Nina ^a   Bakker, Conny T ^b   De Knegt, Robert J ^c   Halley, Dicky J J ^c   Finel, Moshe ^a   Bosma, Piter J ^b  

^a UNIVERSITY OF HELSINKI   (Finland)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

^c ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Bilirubin; CN; Crigler Najjar syndrome; Gilbert syndrome; UGT1A1

Indexed keywords

BILIRUBIN; GLUCURONOSYLTRANSFERASE 1A1; PHENOBARBITAL;

ADOLESCENT; ADULT; ALLELE; ARTICLE; BELGIUM; BILIRUBIN BLOOD LEVEL; CHOLECYSTECTOMY; CLINICAL ARTICLE; CRIGLER NAJJAR SYNDROME; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; ENZYME ACTIVITY; FEMALE; GALLSTONE; GENE MUTATION; GENETIC COUNSELING; GENETIC IDENTIFICATION; GENETIC LINKAGE; GENETIC POLYMORPHISM; GENOTYPE PHENOTYPE CORRELATION; HUMAN; IN VITRO STUDY; MALE; MISSENSE MUTATION; NETHERLANDS; NUCLEOTIDE SEQUENCE; PHOTOTHERAPY; PRIORITY JOURNAL; PROMOTER REGION; SINGLE NUCLEOTIDE POLYMORPHISM; WILD TYPE;

ADOLESCENT; ADULT; ALLELES; ANIMALS; BELGIUM; BILIRUBIN; CELLS, CULTURED; CRIGLER-NAJJAR SYNDROME; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENOTYPE; GLUCURONOSYLTRANSFERASE; HUMANS; HYPERBILIRUBINEMIA; INSECTS; MALE; MIDDLE AGED; MUTATION, MISSENSE; NETHERLANDS; PHENOTYPE; YOUNG ADULT;

EID: 74049099798     PISSN: 10597794     EISSN: None     Source Type: Journal    
DOI: 10.1002/humu.21133     Document Type: Article

References (38)

1. Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O. 1993. Identification of defect in the genes for bilirubin UDPglucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun 197:1239-1244.
2. Arias IM, Gartner LM, Cohen M, Ben-Ezzer J, Levi AJ. 1968. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency: evidence for genetic heterogeneity. Trans Assoc Am Physicians 81:66-75.
3. Bhutani VK, Gourley GR, Adler S, Kreamer B, Dalin C, Johnson LH. 2000. Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia. Pediatrics 106:E17.
4. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de BA, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP. 1995. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 333:1171-1175.
5. Bosma PJ, Chowdhury NR, Goldhoorn BG, Hofker MH, Oude Elferink RP, Jansen PL, Chowdhury JR. 1992a. Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology 15:941-947.
6. Bosma PJ, Chowdhury JR, Huang TJ, Lahiri P, Elferink RP, van Es HH, Lederstein M, Whitington PF, Jansen PL, Chowdhury NR. 1992b. Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I. FASEB J 6:2859-2863.
7. Bosma PJ, Goldhoorn B, Oude Elferink RP, Sinaasappel M, Oostra BA, Jansen PL. 1993. A mutation in bilirubin uridine 50-diphosphate- glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II. Gastroenterology 105:216-220.
8. Bosma PJ, van derMeer I, Bakker CT, Hofman A, Paul-Abrahamse M, Witteman JC. 2003. UGT1A1*28 allele and coronary heart disease: the Rotterdam Study. Clin Chem 49:1180-1181.
9. Brodersen R, Friis-Hansen B, Stern L. 1983. Drug-induced displacement of bilirubin from albumin in the newborn. Dev Pharmacol Ther 6:217-229.
10. Chalasani N, Chowdhury NR, Chowdhury JR, Boyer TD. 1997. Kernicterus in an adult who is heterozygous for Crigler-Najjar syndrome and homozygous for Gilbert-type genetic defect. Gastroenterology 112:2099-2103.
11. Ciotti M, Chen F, Rubaltelli FF, Owens IS. 1998a. Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease. Biochim Biophys Acta 1407:40-50.
12. Ciotti M, Cho JW, George J, Owens IS. 1998b. Required buried alpha-helical structure in the bilirubin UDP-glucuronosyltransferase, UGT1A1, contains a nonreplaceable phenylalanine. Biochemistry 37:11018-11025.
13. Ciotti M, Obaray R, Martin MG, Owens IS. 1997. Genetic defects at the UGT1 locus associated with Crigler-Najjar type I disease, including a prenatal diagnosis. Am J Med Genet 68:173-178.
14. Ciotti M, Yeatman MT, Sokol RJ, Owens IS. 1995. Altered coding for a strictly conserved di-glycine in the major bilirubin UDP-glucuronosyltransferase of a Crigler-Najjar type I patient. J Biol Chem 270:3284-3291.
15. Crawford JM, Ransil BJ, Narciso JP, Gollan JL. 1992. Hepatic microsomal bilirubin UDP-glucuronosyltransferase. The kinetics of bilirubin mono- and diglucur-onide synthesis. J Biol Chem 267:16943-16950.
16. Crigler Jr JF, Najjar VA. 1952. Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 10:169-180.
17. d'Apolito M, Marrone A, Servedio V, Vajro P, De FL, Iolascon A. 2007. Seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia. Haematologica 92:133-134.
18. Gantla S, Bakker CT, Deocharan B, Thummala NR, Zweiner J, Sinaasappel M, Roy CJ, Bosma PJ, Roy CN. 1998. Splice-site mutations: a novel genetic mechanism of Crigler-Najjar syndrome type 1. Am J Hum Genet 62:585-592.
19. Itaaho K, Mackenzie PI, Ikushiro S, Miners JO, Finel M. 2008. The configuration of the 17-hydroxy group variably influences the glucuronidation of beta-estradiol and epiestradiol by human UDP-glucuronosyltransferases. Drug Metab Dispos 36:2307-2315.
20. Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR. 2000. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 16:297-306.
21. Kurkela M, Garcia-Horsman JA, Luukkanen L, Morsky S, Taskinen J, Baumann M, Kostiainen R, Hirvonen J, Finel M. 2003. Expression and characterization of recombinant human UDP-glucuronosyltransferases (UGTs). UGT1A9 is more resistant to detergent inhibition than other UGTs and was purified as an active dimeric enzyme. J Biol Chem 278:3536-3544.
22. Kurkela M, Patana AS, Mackenzie PI, Court MH, Tate CG, Hirvonen J, Goldman A, Finel M. 2007. Interactions with other human UDP- glucuronosyltransferases attenuate the consequences of the Y485D mutation on the activity and substrate affinity of UGT1A6. Pharmacogenet. Genomics 17:115-126.
23. Li Y, Buckley D, Wang S, Klaassen CD, Zhong XB. 2009. Genetic polymorphisms in the TATA box and upstream phenobarbital-responsive enhancer module of the UGT1A1 promoter have combined effects on UGT1A1 transcription mediated by CAR, PXR, or GR in human liver. Drug Metab Dispos 37:1978-1986.
24. Luukkanen L, Mikkola J, Forsman T, Taavitsainen P, Taskinen J, Elovaara E. 2001. Glucuronidation of 1-hydroxypyrene by human liver microsomes and human UDP-glucuronosyltransferases UGT1A6, UGT1A7, and UGT1A9: development of a high-sensitivity glucuronidation assay for human tissue. Drug Metab Dispos 29:1096-1101.
25. Luukkanen L, Taskinen J, Kurkela M, Kostiainen R, Hirvonen J, Finel M. 2005. Kinetic characterization of the 1A subfamily of recombinant human UDPglucuronosyltransferases. Drug Metab Dispos 33:1017-1026.
26. Miley MJ, Zielinska AK, Keenan JE, Bratton SM, Radominska-Pandya A, Redinbo MR. 2007. Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7. J Mol Biol 369:498-511.
27. Moghrabi N, Clarke DJ, Boxer M, Burchell B. 1993. Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2. Genomics 18:171-173.
28. Patana AS, Kurkela M, Goldman A, Finel M. 2007. The human UDP-glucuronosyltransferase: identification of key residues within the nucleotide-sugar binding site. Mol Pharmacol 72:604-611.
29. Poddar B, Bharti B, Goraya J, Parmar VR. 2002. Kernicterus in a child with Crigler-Najjar Syndrome Type II. Trop Gastroenterol 23:33-34.
30. Seppen J, Bosma PJ, Goldhoorn BG, Bakker CT, Chowdhury JR, Chowdhury NR, Jansen PL, Oude Elferink RP. 1994. Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate- glucuronosyltransferase. J Clin Invest 94:2385-2391.
31. Seppen J, Steenken E, Lindhout D, Bosma PJ, Elferink RP. 1996. A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDPglucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II. FEBS Lett 390:294-298.
32. Thapa BR, Yachha SK, Mehta S. 1987. Crigler-Najjar syndrome type II with kernicterus. Indian Pediatr 24:680-683.
33. Tukey RH, Strassburg CP. 2001. Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract. Mol Pharmacol 59:405-414.
34. Udomuksorn W, Elliot DJ, Lewis BC, Mackenzie PI, Yoovathaworn K, Miners JO. 2007. Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenet Genomics 17:1017-1029.
35. Van der Veere CN, Sinaasappel M, McDonagh AF, Rosenthal P, Labrune P, Odievre M, Fevery J, Otte JB, McClean P, Burk G, Masakowski V, Sperl W, Mowat AP, Vergani GM, Heller K,Wilson JP, Shepherd R, Jansen PL. 1996. Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology 24: 311-315.
36. Xiong Y, Patana AS, Miley MJ, Zielinska AK, Bratton SM, Miller GP, Goldman A, Finel M, Redinbo MR, Radominska-Pandya A. 2008. The first aspartic acid of the DQxD motif for human UDP-glucuronosyltransferase 1A10 interacts with UDP-glucuronic acid during catalysis. Drug Metab Dispos 36:517-522.
37. Yamamoto K, Sato H, Fujiyama Y, Doida Y, Bamba T. 1998. 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 1406:267-273.
38. Zmetakova I, Ferak V, Minarik G, Ficek A, Polakova H, Ferakova E, Kadasi L. 2007. Identification of the deletions in the UGT1A1 gene of the patients with Crigler-Najjar syndrome type I from Slovakia. Gen Physiol Biophys 26:306-310.