Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias

Douglas J. Clarke, Nabil Moghrabi, Gemma Monaghan, Andrew Cassidy, Maureen Boxer, Robert Hume, Brian Burchell

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Congenital familial non-haemolytic hyperbilirubinaemias are potentially lethal syndromes caused by genetic lesions that reduce or abolish hepatic bilirubin UDP-glucuronosyltransferase activity. Here we describe genetic defects that occur in the UGT1 gene complex that cause three non-haemolytic unconjugated hyperbilirubinaemia syndromes. The most severe syndrome, termed Crigler-Najjar syndrome type I, is mainly associated with mutations in exons 2 to 5 that affect all UGT1 enzymes and many of the mutations result in termination codons and frameshifts. Crigler-Najjar type II syndrome which is treatable with phenobarbital therapy is associated with less dramatic missense mutations or heterozygous expression of mutant and normal alleles. Gilbert's syndrome, the most prevalent (2-19% in population studies) and mildest of the three syndromes is principally caused by a TA insertion at the TATA promoter region upstream of the UGTIA1 exon. Current methods used for the diagnosis and treatment of these diseases are discussed.

Original languageEnglish
Pages (from-to)63-74
Number of pages12
JournalClinica Chimica Acta
Volume266
Issue number1
DOIs
Publication statusPublished - 9 Oct 1997
Externally publishedYes

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