A New Type of Defect in the Gene for Bilirubin Uridine 5 '-Diphosphate-Glucuronosyltransferase in a Patient with Crigler-Najjar Syndrome Type I
| Autor: | Y. Yamada, Osamu Koiwai, Tsuneo Nakagawa, Hiroshi Sato, Shunji Mimura, Yoshiko Sasaoka, Hiroomi Keino, Sachiko Aono, Shoju Onishi |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Heterozygote DNA Complementary Glucuronosyltransferase Molecular Sequence Data Genes Recessive Biology medicine.disease_cause Autosomal recessive trait Exon Complementary DNA medicine Humans Point Mutation Amino Acid Sequence Gene Crigler-Najjar Syndrome DNA Primers Genetics Mutation Base Sequence Point mutation Homozygote Infant Exons Molecular biology Stop codon Pedigree Pediatrics Perinatology and Child Health biology.protein |
| Zdroj: | Pediatric Research. 35:629-632 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-199406000-00002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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