A mild phenotype of dihydropyrimidine dehydrogenase deficiency and developmental retardation associated with a missense mutation affecting cofactor binding.

ABSTRACT

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.