Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

UDP-Glucuronosyltransferase

Das UGT1A-Gen kodiert die UDP-Glucuronosyltransferase ein Enzym, welches am Bilirubinabbau beteiligt ist. Mutationen führen zu verschiedenen Formen der Hyperbilirubinämie bei welchen das unkonjugierte Bilirubin erhöht gefunden wird. Die Vererbung dieser Erkrankungen ist entweder dominant order rezessiv.

Diagnostik:

Clinic Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5
Probentyp genomic DNA
Clinic Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25
Probentyp genomic DNA

Krankheiten:

Crigler-Najjar-Syndrom 1
UGT1A
Crigler-Najjar-Syndrom 2
UGT1A
Gilbert-Syndrom
UGT1A
Familiäre transiente neonatale Hyperbilirubinämie
UGT1A

Referenzen:

1.

Monaghan G et al. (1999) Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn.

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2.

Maruo Y et al. (1999) A case of anorexia nervosa with hyperbilirubinaemia in a patient homozygous for a mutation in the bilirubin UDP-glucuronosyltransferase gene.

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3.

Kren BT et al. (1999) Correction of the UDP-glucuronosyltransferase gene defect in the gunn rat model of crigler-najjar syndrome type I with a chimeric oligonucleotide.

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4.

Kimura T et al. (1999) Intermittent jaundice in patients with acute leukaemia: a common mutation of the bilirubin uridine-diphosphate glucuronosyltransferase gene among Asians.

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5.

Tukey RH et al. (2000) Human UDP-glucuronosyltransferases: metabolism, expression, and disease.

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6.

Findlay KA et al. (2000) Characterization of the uridine diphosphate-glucuronosyltransferase-catalyzing thyroid hormone glucuronidation in man.

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7.

Kaplan M et al. (2000) Gilbert's syndrome and hyperbilirubinaemia in ABO-incompatible neonates.

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8.

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9.

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10.

Maruo Y et al. (2000) Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene.

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11.

Kadakol A et al. (2001) Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus.

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12.

Premawardhena A et al. (2001) Genetic determinants of jaundice and gallstones in haemoglobin E beta thalassaemia.

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13.

Gong QH et al. (2001) Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus.

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14.

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15.

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16.

Francoual J et al. (2002) Crigler-Najjar syndrome type I in Tunisia may be associated with a founder effect related to the Q357R mutation within the UGT1 gene.

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17.

Labrune P et al. (2002) Association of a homozygous (TA)8 promoter polymorphism and a N400D mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome.

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18.

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19.

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20.

Fertrin KY et al. (2003) UDP-glucuronosyltransferase 1 gene promoter polymorphism is associated with increased serum bilirubin levels and cholecystectomy in patients with sickle cell anemia.

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21.

Ritter JK et al. (1992) A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini.

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22.

Sato H et al. (1992) Mapping of the mouse bilirubin UDP-glucuronosyltransferase gene (Gnt-1) to chromosome 1 by restriction fragment length variations.

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23.

Ohnishi A et al. (2003) Rapid proteasomal degradation of translocation-deficient UDP-glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type II.

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24.

Basu NK et al. (2004) Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake.

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25.

Maruo Y et al. (2003) Co-occurrence of three different mutations in the bilirubin UDP-glucuronosyltransferase gene in a Chinese family with Crigler-Najjar syndrome type I and Gilbert's syndrome.

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26.

Innocenti F et al. (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan.

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27.

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28.

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29.

Roses AD et al. (2004) Pharmacogenetics and drug development: the path to safer and more effective drugs.

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30.

Maruo Y et al. (2004) Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome.

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31.

Kaniwa N et al. (2005) Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American.

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32.

Petit FM et al. (2005) Paternal isodisomy for chromosome 2 as the cause of Crigler-Najjar type I syndrome.

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33.

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34.

Edison ES et al. (2005) Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism.

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35.

Mackenzie PI et al. (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily.

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36.

Bosma PJ et al. (1992) Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I.

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37.

Ritter JK et al. (1992) Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient.

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38.

Petit F et al. (2006) Crigler-Najjar type II syndrome may result from several types and combinations of mutations in the UGT1A1 gene.

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39.

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40.

Mackenzie PI et al. (1990) The cDNA sequence and expression of a variant 17 beta-hydroxysteroid UDP-glucuronosyltransferase.

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41.

Hsieh TY et al. (2007) Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding protein binding affinity of UGT1A1 gene promoter.

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42.

Udomuksorn W et al. (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.

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43.

Girard H et al. (2007) Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity.

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44.

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45.

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46.

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47.

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48.

Wooster R et al. (1991) Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family.

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49.

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50.

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51.

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52.

Lee JS et al. (2011) Genetic variation in UGT1A1 typical of Gilbert syndrome is associated with unconjugated hyperbilirubinemia in patients receiving tocilizumab.

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53.

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54.

Sato H et al. (2013) Association of breast-fed neonatal hyperbilirubinemia with UGT1A1 polymorphisms: 211G>A (G71R) mutation becomes a risk factor under inadequate feeding.

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55.

Zahreddine HA et al. (2014) The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation.

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56.

Jackson MR et al. (1987) Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA.

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57.

Nagai F et al. (1988) Studies on the genetic linkage of bilirubin and androsterone UDP-glucuronyltransferases by cross-breeding of two mutant rat strains.

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58.

Harding D et al. (1988) Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells.

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59.

Peters WH et al. (1984) The molecular weights of UDP-glucuronyltransferase determined with radiation-inactivation analysis. A molecular model of bilirubin UDP-glucuronyltransferase.

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60.

Bosma PJ et al. (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome.

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61.

Erps LT et al. (1994) Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro.

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62.

Aono S et al. (1994) A new type of defect in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase in a patient with Crigler-Najjar syndrome type I.

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63.

Seppen J et al. (1994) Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.

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64.

Gollan JL et al. (1975) Prolonged survival in three brothers with severe type 2 Crigler-Najjar syndrome. Ultrastructural and metabolic studies.

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65.

Moghrabi N et al. (1993) Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syndrome type I: implication in carrier detection and prenatal diagnosis.

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66.

Ritter JK et al. (1993) A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase.

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67.

Moghrabi N et al. (1993) Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2.

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68.

van Es HH et al. (1993) Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37.

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69.

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70.

Koiwai O et al. (1995) Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase.

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71.

Seppen J et al. (1996) A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II.

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72.

Mojarrabi B et al. (1996) cDNA cloning and characterization of the human UDP glucuronosyltransferase, UGT1A3.

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73.

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74.

Strassburg CP et al. (1997) Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue.

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75.

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76.

Kaplan M et al. (1997) Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia.

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77.

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78.

Sampietro M et al. (1997) The expression of uridine diphosphate glucuronosyltransferase gene is a major determinant of bilirubin level in heterozygous beta-thalassaemia and in glucose-6-phosphate dehydrogenase deficiency.

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79.

Iolascon A et al. (1998) UGT1 promoter polymorphism accounts for increased neonatal appearance of hereditary spherocytosis.

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80.

Iyer L et al. (1998) Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes.

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81.

Gantla S et al. (1998) Splice-site mutations: a novel genetic mechanism of Crigler-Najjar syndrome type 1.

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82.

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83.

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84.

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85.

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