Autor(es): Costa, Elísio ; Vieira, Emília ; Martins, Marcia ; Saraiva, Jorge A. ; Cancela, Eugénia ; Costa, Miguel Rocha ; Bauerle, Roswitha ; Freitas, Teresa R. ; Carvalho, João ; Santos-Silva, Ermelinda ; Barbot, José ; Santos, Rosário
Data: 2006
Identificador Persistente: http://hdl.handle.net/10198/491
Origem: Biblioteca Digital do IPB
Assunto(s): Gilbert syndrome; UGT1A1; Crigler–Najjar syndrome; Hyperbilirubinemia; Mutations
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.
