Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2

Journal Article · Fri Oct 01 00:00:00 EDT 1993 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1993.1451· OSTI ID:7159815

Moghrabi, N; Clarke, D J; Boxer, M; Burchell, B ^[1]

---

1. Univ. of Dundee, Scotland (United Kingdom)

Crigler-Najjar syndrome is an inborn error of metabolism that is characterized by severe unconjugated hyperbilirubinemia. The disease is caused by a deficiency in the hepatic enzyme bilirubin UDP-glucoronosyl-transferase (UGT), which is responsible for the safe elimination of the toxic heme breakdown product bilirubin from the body via bile. Two types of the disease have been classified according to their clinical severity. Crigler-Najjar syndrome type 2 (CN-2) is a less severe form of the disease that is caused by a reduced ability to glucoronidate bilirubin, with serium bilirubin levels ranging from 60 to 340 [mu]M. The recent identification of a large gene locus termed UGT1 that encodes two bilirubin UGTs (UGT1*1 and UGT1*4) and two phenol UGTs (UGT1*02 and UGT1*6) has provided the tools for studying hereditary unconjugated hyperbilirubinemias. Recent analysis of five unrelated CN-1 patients has revealed the presence of several mutations in the UGT1 gene complex. Here, the authors present the first report of a mutation identified in a CN-2 patient and discuss the correlation of this mutation with the severity of the disease. The missense mutation identified in exon 2 of the CN-2 patient's DNA that is shared by several UGT1 genes is predicted to change a glutamine codon (CAG) to an arginine codon (CGG) at residue 331 of the bilirubin UGT isoenzymes, UGT1*1 and UGT1*4, and residue 329 of UGT1*02 and residue 327 of UGT1*6 of the phenol UGT isoenzymes. This agreed with enzymological and immunochemical studies, which demonstrated that the expression of all UGT1 proteins was affected in the CN-2 patient. 12 refs., 1 fig.

• OSTI ID: 7159815
• Journal Information: Genomics; (United States), Vol. 18:1; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BILIRUBIN
METABOLIC DISEASES
GENE MUTATIONS
DETECTION
GLYCOSYL TRANSFERASES
AZOLES
CARBOXYLIC ACIDS
DISEASES
ENZYMES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PROTEINS
PYRROLES
TRANSFERASES
550400* - Genetics
550200 - Biochemistry
550900 - Pathology