title: Identification of a novel mutation in UDP-glucuronosyltransferase (UGT1A1) gene in a child with neonatal unconjugated hyperbilirubinemia.
abstract: Genetic alterations of the UGT1A1 gene result in Crigler-Najjar (CNS) and Gilbert's (GS)-Syndromes, two autosomal recessive conditions characterized by non-hemolytic unconjugated hyperbilirubinemia. While GS is characterized by mild hyperbilirubinemia, CNS is classified as follows: type I (CNS-I), often associated with irreversible neurological damage due to total deficiency of the UGT1A1 enzyme activity, and type II (CNS-II) where a minimal level of UGT1A1 enzyme activity is maintained. In this context, differential diagnosis of CNS forms needs to be supported by clinical molecular laboratory, in order to correlate biochemical findings to specific genetic mutations. Our paper describes in detail the peculiar clinical feature found in a child with severe neonatal unconjugated hyperbilirubinemia, where DNA analysis showed a new compound heterozygosis determined by two mutations, a known (c.508_510delTTC) and a novel mutation (c.1099C>T) giving a genotype compatible with clinical picture of CNS-II. This novel genotype extends the spectrum of known UGT1A1 mutations, which, in our opinion, could be higher than that currently reported in the literature. Finally, genetic analysis may also be helpful for patients' management.
authors.affiliation: Laboratory of Clinical Molecular Diagnostics, Department of Biochemistry & Clinical Biochemistry, Catholic University, Rome, Italy. angelo.minucci@virgilio.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Minucci
authors.forename: Giulia
authors.initials: G
authors.lastname: Canu
authors.forename: Leonarda
authors.initials: L
authors.lastname: Gentile
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cimino
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zuppi
authors.forename: Ettore
authors.initials: E
authors.lastname: Capoluongo
mesh_terms: D003414:Crigler-Najjar Syndrome / Q000209:etiology; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000209:etiology / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme