RESUMO
OBJECTIVES: Evaluation of a non-synonymous mutation associated with dihydropyrimidine dehydrogenase (DPD) deficiency. DESIGN AND METHODS: DPD enzyme analysis, mutation analysis and molecular dynamics simulations based on the 3D-model of DPD. RESULTS: The substitution Lys63Glu is likely to affect the FAD binding pocket within the DPD protein and contributes to a near-complete DPD deficiency in a patient with developmental retardation. CONCLUSIONS: Like other DPD variants attenuating FAD binding, Lys63Glu should be included in screening for DPD deficiency.
Assuntos
Deficiência da Di-Hidropirimidina Desidrogenase/urina , Di-Hidrouracila Desidrogenase (NADP)/genética , Flavina-Adenina Dinucleotídeo/metabolismo , Mutação de Sentido Incorreto/genética , Sequência de Aminoácidos , Criança , Creatinina/urina , Di-Hidrouracila Desidrogenase (NADP)/química , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Ligação Proteica/genética , Ligação Proteica/fisiologia , Homologia de Sequência de Aminoácidos , Timina/urina , Uracila/análogos & derivados , Uracila/urinaRESUMO
The Wiskott-Aldrich syndrome is an X-linked hereditary disorder associated with combined immunodeficiency, thrombocytopenia, small platelets, eczema, and increased susceptibility to autoimmune disorders and cancers. It is caused by mutations in the gene (WAS) for the Wiskott-Aldrich syndrome protein (WASP). We investigated family members of the patients originally described by Wiskott in 1937 and identified a new frame shift mutation in exon 1 of WAS. This mutation is likely to be the hypothesized genotype that caused the severe form of the Wiskott-Aldrich syndrome in the three brothers described by Wiskott.
