title: Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes.
abstract: We describe the molecular study in a cohort of 120 Portuguese patients with the clinical diagnosis of Gilbert syndrome and in one with the diagnosis of Crigler-Najjar syndrome type II, as well as a prenatal diagnosis of Crigler-Najjar syndrome type I. Among the 120 unrelated patients with Gilbert syndrome, 110 were homozygous for the [TA]7 allele ([TA]7/[TA]7), and one patient was a compound heterozygote for two different insertions ([TA]7/[TA]8). The remaining 9 patients were heterozygous for the TA insertion ([TA]6/[TA]7). Additional studies in these 9 patients revealed heterozygosity for the c.674T>G, c.488_491dupACCT and c.923G>A mutations, in 1, 1 and 4 patients, respectively. The patient with Crigler-Najjar syndrome type II was a compound heterozygote for [TA]7 and the c.923G>A mutation. The undocumented polymorphisms c.-1126C>T and c.997-82T>C were also detected in the course of this study. Prenatal diagnosis in a family with a boy previously diagnosed as Crigler-Najjar syndrome type I and homozygosity for the c.923G>A mutation revealed that the fetus was unaffected. Homozygosity for the [TA] insertion was found to be the most frequent cause of GS in our population. Identification of further mutations in the UGT1A1 gene was also seen to contribute significantly towards diagnosis.
authors.affiliation: Escola Superior de Saúde, Instituto Politécnico de Bragança, Avenida D. Afonso V, 5300-121 Bragança, Portugal. elisio.costa@ipb.pt
authors.forename: Elísio
authors.initials: E
authors.lastname: Costa
authors.forename: Emília
authors.initials: E
authors.lastname: Vieira
authors.forename: Marcia
authors.initials: M
authors.lastname: Martins
authors.forename: Jorge
authors.initials: J
authors.lastname: Saraiva
authors.forename: Eugénia
authors.initials: E
authors.lastname: Cancela
authors.forename: Miguel
authors.initials: M
authors.lastname: Costa
authors.forename: Roswitha
authors.initials: R
authors.lastname: Bauerle
authors.forename: Teresa
authors.initials: T
authors.lastname: Freitas
authors.forename: João R
authors.initials: JR
authors.lastname: Carvalho
authors.forename: Ermelinda
authors.initials: E
authors.lastname: Santos-Silva
authors.forename: José
authors.initials: J
authors.lastname: Barbot
authors.forename: Rosário
authors.initials: R
authors.lastname: Dos Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003414:Crigler-Najjar Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005878:Gilbert Disease / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme