title: Identification of two novel mutations C79X and R235Q in the dihydropyrimidine dehydrogenase gene in a patient presenting with hematuria.
abstract: A patient with hematuria was shown to have thymine-uraciluria. The dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells was 0.16 nmol/mg/h; controls: 9.9 +/- 2.8 nmol/mg/h. Analysis of DPYD showed that the patient was compound heterozygous for the novel mutations 237C > A (C79X) in exon 4 and 704G > A (R235Q) in exon 7. The nonsense mutation (C79X) leads to premature termination of translation and thus to a non-functional protein. Analysis of the crystal structure of pig DPD suggested that the R235Q mutation might interfere with the binding of FAD and the electron flow between the NADPH and the pyrimidine substrate site of DPD.
authors.affiliation: Academic Medical Center, Department of Clinical Chemistry, University of Amsterdam, Emma Children's Hospital, Amsterdam, The Netherlands. a.b.vankuilenburg@amc.uva.nl
authors.forename: A B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.forename: J
authors.initials: J
authors.lastname: Meijer
authors.forename: D
authors.initials: D
authors.lastname: Dobritzsch
authors.forename: B
authors.initials: B
authors.lastname: Lohkamp
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: J
authors.initials: J
authors.lastname: Roelofsen
authors.forename: N G G M
authors.initials: NG
authors.lastname: Abeling
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: C
authors.initials: C
authors.lastname: Buzing
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D018360:Crystallography, X-Ray; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006417:Hematuria / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D017354:Point Mutation; D011487:Protein Conformation; D013552:Swine
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP)