TY - JOUR T1 - Mutations in the urocanase gene <em>UROC1</em> are associated with urocanic aciduria JF - Journal of Medical Genetics JO - J Med Genet SP - 407 LP - 411 DO - 10.1136/jmg.2008.060632 VL - 46 IS - 6 AU - C Espinós AU - M Pineda AU - D Martínez-Rubio AU - V Lupo AU - A Ormazabal AU - M A Vilaseca AU - L J M Spaapen AU - F Palau AU - R Artuch Y1 - 2009/06/01 UR - http://jmg.bmj.com/content/46/6/407.abstract N2 - 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. ER -