Abstract |
At least three types of congenital nonhemolytic unconjugated hyperbilirubinemias, including the rare Crigler-Najjar (CN) diseases (Types I or II) and Gilbert's syndrome (affecting 6% of the population) are associated with either absent or reduced hepatic UDP-glucuronosyltransferase ( transferase) activity towards the potentially toxic endogenous acceptor, bilirubin. Here, we review the biochemical studies associated with these deficiencies. Accumulated evidence from studies with an animal model of CN Type I syndrome, the Gunn strain of hyperbilirubinemic rats, suggested that multiple isozymes are absent. These confounding observations have been clarified by a flurry of reports which have revealed the molecular basis for the complex disease phenotype in the Gunn rat and by the isolation and description of a novel human gene complex, UGT1, which encodes multiple and independently-regulated transferase isozymes that contain identical carboxyl terminal regions (246 amino acids). Finally, we discuss the implications of the gene organization and genetic defects determined for four different CN Type I individuals as a basis for a model which explains the inheritance pattern and genotypes of other familial unconjugated hyperbilirubinemias.
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Authors | I S Owens, J K Ritter |
Journal | Pharmacogenetics
(Pharmacogenetics)
Vol. 2
Issue 3
Pg. 93-108
(Jun 1992)
ISSN: 0960-314X [Print] England |
PMID | 1306114
(Publication Type: Journal Article, Review)
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Chemical References |
- bilirubin glucuronoside glucuronosyltransferase
- DNA
- Glucuronosyltransferase
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Topics |
- Animals
- Cloning, Molecular
- Crigler-Najjar Syndrome
(enzymology, genetics)
- DNA
(genetics)
- Female
- Gilbert Disease
(enzymology, genetics)
- Glucuronosyltransferase
(genetics)
- Humans
- Hyperbilirubinemia, Hereditary
(enzymology, genetics)
- Male
- Multigene Family
- Pedigree
- Phenotype
- Rats
- Rats, Gunn
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