Mutations in the urocanase gene UROC1 are associated with urocanic aciduria
| Autor: | Leo J M Spaapen, Vincenzo Lupo, Aida Ormazabal, Mercè Pineda, Carmen Espinós, Rafael Artuch, Francesc Palau, Dolores Martínez-Rubio, Maria Antonia Vilaseca |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmg.2008.060632 |
| Popis: | 22 p., figuras y bibliografía Urocanase is an enzyme in the histidine pathway encoded by the UROC1 gene. We describe the first putative mutations, p.L70P and p.R450C, in the coding region of the UROC1 gene in a girl who suffers from urocanic aciduria presenting with mental retardation and intermittent ataxia. 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 imply 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 the patient. This work was supported by grants from the Fondo de Investigación Sanitaria (PI051318 and PI070548). The CIBERER is an initiative of the Instituto de Salud Carlos III. |
| Databáze: | OpenAIRE |
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