Mutations in the urocanase gene UROC1 are associated with urocanic aciduria

• Published in: Journal of medical genetics Vol. 46; no. 6; pp. 407 - 411
• Main Authors: Espinós, C, Pineda, M, Martínez-Rubio, D, Lupo, V, Ormazabal, A, Vilaseca, M A, Spaapen, L J M, Palau, F, Artuch, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.06.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Sequence; Ataxia; Automation; Biological and medical sciences; Biomarkers - cerebrospinal fluid; Child; Computer Simulation; Female; Folic Acid - cerebrospinal fluid; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic engineering; Genetics of eukaryotes. Biological and molecular evolution; Histidine - metabolism; Humans; Intellectual disabilities; Intellectual Disability - genetics; Medical genetics; Medical sciences; Metabolites; Models, Molecular; Molecular and cellular biology; Molecular Sequence Data; Mutation; Sequence Alignment; Urine; Urocanate Hydratase - chemistry; Urocanate Hydratase - deficiency; Urocanate Hydratase - genetics; Urocanic Acid - urine; Human; Association; Urocanate hydratase; Gene; Enzyme; Aciduria; Genetics; Lyases; Mutation; Carbon-oxygen lyases; Hydro-lyases
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg.2008.060632

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 α-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.