title: Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II.
abstract: Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepatic bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase activity. Recently, there has been progress in mutation analysis of patients with CN type II. Here, we analyzed both the coding and the promoter regions of the gene in seven Japanese patients with CN type II from five unrelated families. The mutations found in this study were classified into three types. The first type was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in exons 1 and 5. These mutations, which were detected in five patients from three unrelated families, were the commonest. The second type, which was detected in one patient, consisted of a single homozygous missense mutation (Arg209Trp) in exon 1. The third type, which was detected in one patient and was a new type of mutation combination, was composed of a homozygous insertion mutation of the TATAA element and a heterozygous missense mutation (Pro229Gln) in exon 1. Although the first and the second type of mutations are recessive, the third type appears to be dominant with incomplete penetrance, since the allele frequency of the insertion mutation of the TATAA element is very high (40%).
authors.affiliation: Second Department of Internal Medicine, Shiga University of Medical Science, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Soeda
authors.forename: T
authors.initials: T
authors.lastname: Kamisako
authors.forename: H
authors.initials: H
authors.lastname: Hosaka
authors.forename: M
authors.initials: M
authors.lastname: Fukano
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: Y
authors.initials: Y
authors.lastname: Satoh
authors.forename: T
authors.initials: T
authors.lastname: Bamba
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D003414:Crigler-Najjar Syndrome / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005796:Genes; D005799:Genes, Dominant; D005808:Genes, Recessive; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: C019787:bilirubin glucuronoside glucuronosyltransferase; D004247:DNA; D014453:Glucuronosyltransferase