Abstract
ABSTRACT: Crigler-Najjar syndrome (CN) type I, which is characterized by the complete absence of bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT) activity, is inherited as an autosomal recessive trait associated with unconjugated hyperbilirubinemia. Phenobarbital has no effect on the bilirubin concentration in the serum of patients with CN type I. Recently, cDNA for two human liver bilirubin UGT (UGT1A and UGT1D) were isolated, and their genetic organization was determined. The UGT1A (UGT1*1) and UGT1D (UGT1*4) genes each have a unique exon 1, whereas exons 2–5 are common to both genes. It has been predicted that some defect in the exons common to both genes is responsible for the absence of UGT1A and UGT1D activities in CN type I, and five cases with such a mutation have been reported. We describe here a new type of defect in the gene for bilirubin UGT in a patient with CN type I, namely, an abnormality in the exon 1 that is characteristic of the UGT1A gene. This mutation is a single nucleotide substitution, that is, C is changed to A at base position 840 in UGT1A cDNA, and this change results in a stop codon. Our patient is homozygous for the defect, and his nonconsanguineous parents and elder brother, who are clinically normal, are heterozygous for the defective allele. No mutation was detected in any exons of the UGT1D gene. Our results suggest that a homozygous nonsense or deletion mutation is detected not only in the exons common to UGT1A and UGT1D genes but also in unique exon 1 of UGT1A in CN type I.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Aono, S., Yamada, Y., Keino, H. et al. A New Type of Defect in the Gene for Bilirubin Uridine 5 '-Diphosphate-Glucuronosyltransferase in a Patient with Crigler-Najjar Syndrome Type I. Pediatr Res 35, 629–632 (1994). https://doi.org/10.1203/00006450-199406000-00002
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199406000-00002
This article is cited by
-
Truncated UDP-glucuronosyltransferase (UGT) from a Crigler–Najjar syndrome type II patient colocalizes with intact UGT in the endoplasmic reticulum
Journal of Human Genetics (2014)
-
Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs: implication of defects in the UGT1A1 gene promoter
Naunyn-Schmiedeberg's Archives of Pharmacology (2008)
-
Family 1 uridine-5′-diphosphate glucuronosyltransferases (UGT1A): from Gilbert’s syndrome to genetic organization and variability
Archives of Toxicology (2008)
-
Pharmacogenomics of human UDP-glucuronosyltransferase enzymes
The Pharmacogenomics Journal (2003)
-
Three Japanese patients with Crigler-Najjar syndrome type I carry an identical nonsense mutation in the gene for UDP-glucuronosyltransferase
Japanese journal of human genetics (1995)
