Mutations in the urocanase gene UROC1 are associated with urocanic aciduria.
J Med Genet
; 46(6): 407-11, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19304569
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Urocanato Hidratase
/
Ácido Urocânico
/
Erros Inatos do Metabolismo dos Aminoácidos
/
Mutação
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
/
Female
/
Humans
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Espanha