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Mutations in the urocanase gene UROC1 are associated with urocanic aciduria
  1. C Espinós1,
  2. M Pineda2,
  3. D Martínez-Rubio1,
  4. V Lupo1,
  5. A Ormazabal2,
  6. M A Vilaseca2,
  7. L J M Spaapen3,
  8. F Palau1,
  9. R Artuch2
  1. 1
    Laboratory of Genetics and Molecular Medicine, Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), and CIBER de Enfermedades Raras (CIBERER), Valencia, Spain
  2. 2
    Pediatric Neurology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, and CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain
  3. 3
    Department of Biochemical Genetics, University Hospital Maastricht, The Netherlands
  1. Dr R Artuch, Clinical Biochemistry Department, Hospital Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain; rartuch{at}hsjdbcn.org

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 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.

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Footnotes

  • Funding: This work was supported by grants from the Fondo de Investigación Sanitaria (PI051318 and PI070548).

  • Competing interests: None declared.

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