[Refinement and role of the diagnosis of Gilbert disease with molecular biology]. / Mise au point et intérêt du diagnostic de la maladie de Gilbert par biologie moléculaire.

ABSTRACT

Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1). Recently, the genetic basis of GS has been identified in caucasian populations it is related to the insertion of a dinucleotide (TA) in the promoter region of the UGT1A1 gene. In Asian populations, GS is due to missense mutations (either homozygous or heterozygous) in the coding sequence. The aim of this study was to develop a simple and rapid method to detect both genetic polymorphisms and mutations. This technique was performed (1) to explore unrelated unconjugated hyperbilirubinemia; (2) to evaluate the frequency of GS in a population of 97 healthy caucasian volunteers 17% of them were homozygous for the TA7/TA7 polymorphism; (3) to determine the incidence of this syndrome in a population of 105 neonates with unconjugated hyperbilirubinemia. The incidence of GS (15%) was not significantly higher than it was in the control group. A correlation between GS genotype and neonatal jaundice was not established; (4) to seek a relationship between GS and preeclampsia with or without Hellp syndrome. The incidence in the Hellp syndrome group (n = 19) was 26%, two fold higher than in preeclampsia group (n = 22) and control group (n = 50) with only 14% and 13% respectively, (5) to start a study regarding the toxicity of irinotecan treatment in a population of homozygous children for the UGT1A1 polymorphism.