title: Identification of the deletions in the UGT1A1 gene of the patients with Crigler-Najjar syndrome type I from Slovakia.
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).
authors.affiliation: Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Mlynská dolina B2-210, 842 15 Bratislava, Slovakia. izmetakova@centrum.sk
authors.forename: I
authors.initials: I
authors.lastname: Zmetáková
authors.forename: V
authors.initials: V
authors.lastname: Ferák
authors.forename: G
authors.initials: G
authors.lastname: Minárik
authors.forename: A
authors.initials: A
authors.lastname: Ficek
authors.forename: H
authors.initials: H
authors.lastname: Poláková
authors.forename: E
authors.initials: E
authors.lastname: Feráková
authors.forename: L
authors.initials: L
authors.lastname: Kádasi
mesh_terms: D000293:Adolescent; D000328:Adult; D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D002648:Child; D003241:Consanguinity; D003414:Crigler-Najjar Syndrome / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007647:Kernicterus / Q000235:genetics; D008297:Male; D006178:Romani People; D017422:Sequence Analysis, DNA; D035781:Siblings; D018154:Slovakia
chemical_list: D014453:Glucuronosyltransferase; D001663:Bilirubin