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

作者：Weidensee Sabine; Goettig Peter; Bertone Marko; Haas Dorothea; Magdolen Viktor; Kiechle Marion; Meindl Alfons; van Kuilenburg Andre B P; Gross Eva^*

来源：Clinical Biochemistry, 2011, 44(8-9): 722-724.

DOI：10.1016/j.clinbiochem.2011.03.033

• DPD deficiency
• DPYD
• Protein structure
• Developmental retardation

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.

• 出版日期2011-6