title: The combination of new missense mutation with [A(TA)7TAA] dinucleotide repeat in UGT1A1 gene promoter causes Gilbert's syndrome.
abstract: Gilbert's syndrome is a benign form of unconjugated hyperbilirubinemia caused by reduction of hepatic activity of bilirubin glucuronosyltranferase. The most common genotype of Gilbert's syndrome is the homozygous polymorphism [A(TA)7TAA] in the promoter of the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1), which results in a decrease in UGT1A1 activity. However, individuals with normal bilirubin levels and no clinical symptoms of Gilbert's syndrome may also present this in a homozygous condition. By direct sequencing, we performed UGT1A1 gene analysis on a 31-year-old man with Gilbert's syndrome and homozygous for [A(TA)7TAA], and on his parents. Two UGT1A1 mutations were identified. Both mutations were inherited from each of the two parents, both with normal levels of bilirubin. One of the two mutations, c.993 (p.Q331H), is a missense mutation and is predicted to have a deleterious effect on protein functionality. Given the importance for clinicians to consider the Gilbert genotype in cases with unexplained indirect hyperbilirubinemia, the case we report may add a new variant to the spectrum of mutations of Gilbert's syndrome.
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Messina, Italy IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: D'Angelo
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Messina, Italy IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Rinaldi
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Messina, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Donato
authors.affiliation: Department of Experimental Sciences Medical-Surgical, Specialist and Odontostomatologic, University of Messina, Messina, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Nicocia
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Messina, Italy IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy antonella.sidoti@unime.it.
authors.forename: Antonina
authors.initials: A
authors.lastname: Sidoti
mesh_terms: D000328:Adult; D003198:Computer Simulation; D018900:Dinucleotide Repeats / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005878:Gilbert Disease / Q000201:enzymology* / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011401:Promoter Regions, Genetic; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D050505:Mutant Proteins; D000099148:UGT1A1 Enzyme
keywords: Gilbert’s syndrome; Hyperbilirubinemia; Mutation analysis; UDP-glucuronosyltransferase; UGT1A1