Identification of the deletions in the UGT1A1 gene of the patients with Crigler-Najjar syndrome type I from Slovakia

Gen Physiol Biophys. 2007 Dec;26(4):306-10.

Abstract

Crigler-Najjar syndrome type I (CN I) is a rare autosomal recessive disorder due to hepatic dysfunction of uridine diphospho-glucuronosyltransferase (UGT) activity toward bilirubin. Complete inactivation of this enzyme causing CN I lead to accumulation of unconjugated bilirubin in serum and bile. Here we report the results of the molecular characterization of the uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene in a consanguineous family of Slovak Roms and an unrelated non-Romany family with CN I. Sequence analysis of UGT1A1 gene in all four Romany patients showed mutation in exon 4, a deletion of an A at codon 407 (1220delA), not yet described in homozygous status. All analysed patients were homozygous for 1220delA mutation and their 3 healthy sibs were heterozygous. The non-Romany patient was a compound heterozygote for two different deletions, 1220delA and 717-718delAG at codon 239. In the family of his cousin a son was born affected with CN I, who was homozygote for 717-718delAG mutation. His other niece affected with CN II was heterozygote for mutation 717-718delAG but homozygote for TA insertion and enhancer substitution T-3279G. Haplotype analysis suggests that the 1220delA mutation is identical by descent in both families, though they originate from two ethnically different populations (Slovaks vs. Roms).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bilirubin / blood
  • Bilirubin / metabolism
  • Child
  • Consanguinity
  • Crigler-Najjar Syndrome / enzymology*
  • Crigler-Najjar Syndrome / genetics*
  • Female
  • Gene Deletion*
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / metabolism
  • Humans
  • Infant, Newborn
  • Kernicterus / genetics
  • Male
  • Roma
  • Sequence Analysis, DNA
  • Siblings
  • Slovakia

Substances

  • Glucuronosyltransferase
  • Bilirubin