Analysis of bilirubin UDP-glucuronosyltransferase gene mutations in an unusual Crigler-Najjar syndrome patient
- Authors:
- Wei-Liang Liu
- Fang Li
- Zhi-Xu He
- Hong-Yu Jiang
- Rong Ai
- Xiao-Xia Chen
- Kang Huang
View Affiliations
Affiliations: Department of Pediatrics, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, P.R. China, Department of Ophthalmology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, P.R. China
- Published online on: June 15, 2012 https://doi.org/10.3892/mmr.2012.950
-
Pages:
667-669
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Abstract
Crigler-Najjar (CN) syndrome is a rare autosomal recessive inherited disorder characterized by non-hemolytic, unconjugated hyperbilirubinemia. The levels of serum bilirubin and the response to phenobarbital treatment have been used to classify CN syndrome into two types: CN I and II. Mutations of the UGT1A1 gene have been found to be responsible for cases of CN syndrome. In the present study, the clinical features of a boy with an unusual type of CN syndrome were analysed. A DNA sample was obtained from the patient, and the promoter region, the exons and flanking intronic sequences of the UGT1A1 gene were analysed using the polymerase chain reaction and sequencing. The case was similar to CN type I in clinical features, but the therapeutic efficacy in the patient was superior to that typically observed in CN type II disease. Sequencing revealed compound heterozygous mutations, c.211G>A (p.G71R), c.1470C>T (p.D490D) and a normal homozygous A[TA]6TAA. No similar case has been reported worldwide and, considering the specific clinical features and therapeutic efficacy, a distinct type of CN was suspected. The phenotype of this unusual CN syndrome patient may be associated with the specific genotype.
View References
|
1
|
Crigler JF and Najjar VA: Congenital
familial non-hemolytic jaundice with kernicterus. Pediatrics.
10:169–179. 1952.PubMed/NCBI
|
|
2
|
Servedio V, d’Apolito M, Maiorano N, et
al: Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome
patients: identification of twelve novel alleles and
genotype-phenotype correlation. Hum Mutat. 25:3252005. View Article : Google Scholar : PubMed/NCBI
|
|
3
|
Aono S, Yamada Y, Keino H, et al:
Identification of defect in the genes for bilirubin
UDP-glucuronosyl-transferase in a patient with Crigler-Najjar
syndrome type II. Biochem Biophys Res Commun. 197:1239–1244. 1993.
View Article : Google Scholar : PubMed/NCBI
|
|
4
|
Aono S, Yamada Y, Keino H, et al: A new
type of defect in the gene for bilirubinuridine
5′-diphosphate-glucuronosyltransferase in a patient with
Crigler-Najjar syndrome type I. Pediatr Res. 6:629–632. 1994.
|
|
5
|
Bosma PJ, Roy Chowdhury N, Goldhoorn BG,
et al: Sequence of exons and 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. 1992. View Article : Google Scholar : PubMed/NCBI
|
|
6
|
Ritter JK, Yeatman MT, Ferreira P, et al:
Identification of a genetic alteration in the code for bilirubin
UDP-glucuronosyltransferase in the UGT1 gene complex of a
Crigler-Najjar type I patient. J Clin Invest. 9:150–155. 1992.
View Article : Google Scholar : PubMed/NCBI
|
|
7
|
Kadakol A, Ghosh SS, Sappal BS, et al:
Genetic lesions of bilirubin-diphosphoglucuronate
glucosyltransferase (UGT1A1) causing Crigler-Najjar Gilbert
syndromes: correlation of genotype to phenotype. Hum Mutat.
4:297–306. 2000. View Article : Google Scholar
|
|
8
|
Akaba K, Kimura T, Sasaki A, et al:
Neonatal hyperbilirubinemia and mutation of the bilirubin uridine
diphosphate-glucuronosyltransferase gene: a common missense
mutation among Japanese, Koreans and Chinese. Biochem Mol Biol Int.
46:21–26. 1998.
|
|
9
|
Kakadol A, Sappal BS, Ghosh SS, et al:
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. J Med Genet. 38:244–249. 2001. View Article : Google Scholar
|
