title: A mild phenotype of dihydropyrimidine dehydrogenase deficiency and developmental retardation associated with a missense mutation affecting cofactor binding.
abstract: OBJECTIVE
  Evaluation of a non-synonymous mutation associated with dihydropyrimidine dehydrogenase (DPD) deficiency.
  
  
  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.
authors.affiliation: Gemeinschaftspraxis für Humangenetik Demuth und Weidensee, D-99084 Erfurt, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Weidensee
authors.forename: Peter
authors.initials: P
authors.lastname: Goettig
authors.forename: Marko
authors.initials: M
authors.lastname: Bertone
authors.forename: Dorothea
authors.initials: D
authors.lastname: Haas
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
authors.forename: Marion
authors.initials: M
authors.lastname: Kiechle
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.forename: Eva
authors.initials: E
authors.lastname: Gross
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D003404:Creatinine / Q000652:urine; D054067:Dihydropyrimidine Dehydrogenase Deficiency / Q000652:urine*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013941:Thymine / Q000652:urine; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine
chemical_list: C007419:dihydrouracil; D005182:Flavin-Adenine Dinucleotide; D014498:Uracil; D003404:Creatinine; D042943:Dihydrouracil Dehydrogenase (NADP); D013941:Thymine