Abstract |
Crigler-Najjar syndrome type I is a severe form of hereditary unconjugated hyperbilirubinemia and is caused by homozygous or compound heterozygous mutations of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). We analyzed the bilirubin UDP-glucuronosyltransferase gene in a female Chinese patient with Crigler-Najjar syndrome type I. Relatives of the patient were also analyzed. The patient was homozygous for a nonsense mutation of R341X. The patient's father, sister and brother, all diagnosed with Gilbert's syndrome, were compound heterozygotes of R341X, P229Q, and an insertion mutation of the TATA box [A(TA)7TAA]. Heterozygotes of nonsense mutations (Q331X and C280X) in our previous study had either Crigler-Najjar syndrome type II or Gilbert's syndrome, but heterozygotes of R341X (mother and grandmothers) were normal. An in vitro expression study of homozygous and heterozygous models of R341X showed 0 and 58%, respectively, of normal enzyme activity. Therefore, the present results indicate that carriers of the nonsense mutation could be normal for plasma bilirubin concentration, Gilbert's syndrome and Crigler-Najjar syndrome type II. The results also suggest the importance of the accumulation of prevalent or polymorphic mutation in the etiology of Gilbert's syndrome and Crigler-Najjar syndrome type II.
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Authors | Y Maruo, K K-H Poon, M Ito, M Iwai, H Takahashi, A Mori, H Sato, Y Takeuchi |
Journal | Clinical genetics
(Clin Genet)
Vol. 64
Issue 5
Pg. 420-3
(Nov 2003)
ISSN: 0009-9163 [Print] Denmark |
PMID | 14616765
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Codon, Nonsense
- bilirubin glucuronoside glucuronosyltransferase
- Glucuronosyltransferase
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Topics |
- Adult
- Amino Acid Substitution
- Base Sequence
- Child, Preschool
- China
(ethnology)
- Codon, Nonsense
- Consanguinity
- Crigler-Najjar Syndrome
(genetics)
- Female
- Gene Transfer Techniques
- Genetic Vectors
- Gilbert Disease
(genetics)
- Glucuronosyltransferase
(genetics)
- Humans
- Male
- Mutation
- Pedigree
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