title: Mutations in the urocanase gene UROC1 are associated with urocanic aciduria.
abstract: Urocanase is an enzyme in the histidine pathway encoded by the UROC1 gene. This report describes the first putative mutations, p.L70P and p.R450C, in the coding region of the UROC1 gene in a girl with urocanic aciduria presenting with mental retardation and intermittent ataxia. Computed (in silico) predictions, protein expression studies and enzyme activity assays suggest that none of the mutations can produce a fully functional enzyme. The p.L70P substitution, which probably implies the disruption of an alpha-helix in the N-terminus, would alter its properties and therefore, its function. The p.R450C change would render impossible any interaction between urocanase and its substrate and would loss its enzyme activity. Consequently, these studies suggest that both mutations could alter the correct activity of urocanase, which would explain the clinical and biochemical findings described in this patient.
authors.affiliation: Clinical Biochemistry Department, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Espinós
authors.forename: M
authors.initials: M
authors.lastname: Pineda
authors.forename: D
authors.initials: D
authors.lastname: Martínez-Rubio
authors.forename: V
authors.initials: V
authors.lastname: Lupo
authors.forename: A
authors.initials: A
authors.lastname: Ormazabal
authors.forename: M A
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: L J M
authors.initials: LJ
authors.lastname: Spaapen
authors.forename: F
authors.initials: F
authors.lastname: Palau
authors.forename: R
authors.initials: R
authors.lastname: Artuch
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D000595:Amino Acid Sequence; D001259:Ataxia; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002648:Child; D003198:Computer Simulation; D005260:Female; D005492:Folic Acid / Q000134:cerebrospinal fluid; D006639:Histidine / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D014559:Urocanate Hydratase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D014560:Urocanic Acid / Q000652:urine*
chemical_list: D015415:Biomarkers; D006639:Histidine; D005492:Folic Acid; D014559:Urocanate Hydratase; D014560:Urocanic Acid