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

Clinical Biochemistry

Volumn 44, Issue 8-9, 2011, Pages 722-724

  Weidensee, Sabine ^a   Goettig, Peter ^b,f   Bertone, Marko ^c   Haas, Dorothea ^d   Magdolen, Viktor ^c   Kiechle, Marion ^c   Meindl, Alfons ^c   van Kuilenburg, André B P ^e   Gross, Eva ^c  

^a Gemeinschaftspraxis für Humangenetik Demuth und Weidensee   (Germany)

^b Department of Biochemistry ^*  (Germany)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^d UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^e UNIVERSITY OF AMSTERDAM   (Netherlands)

^f UNIVERSITY OF SALZBURG   (Austria)

Author keywords

Developmental retardation; DPD deficiency; DPYD; Protein structure

Indexed keywords

DIHYDROPYRIMIDINE DEHYDROGENASE; FLAVINE ADENINE NUCLEOTIDE; GLUTAMIC ACID; LYSINE;

ARTICLE; DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY; ENZYME ANALYSIS; GROWTH RETARDATION; HUMAN; MISSENSE MUTATION; MOLECULAR DYNAMICS; MUTATIONAL ANALYSIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; SIMULATION;

AMINO ACID SEQUENCE; CHILD; CREATININE; DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY; DIHYDROURACIL DEHYDROGENASE (NADP); FLAVIN-ADENINE DINUCLEOTIDE; GENOTYPE; HUMANS; MALE; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; PROTEIN BINDING; SEQUENCE HOMOLOGY, AMINO ACID; THYMINE; URACIL;

EID: 79955838788     PISSN: 00099120     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.clinbiochem.2011.03.033     Document Type: Article

References (11)

1. Schnackerz K.D., Dobritzsch D., Lindqvist Y., Cook P.F. Dihydropyrimidine dehydrogenase: a flavoprotein with four iron-sulfur clusters. Biochim Biophys Acta 2004, 1701:61-74.
2. van Kuilenburg A.B., Vreken P., Abeling N.G., et al. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet 1999, 104:1-9.
3. van Kuilenburg A.B., Meijer J., Mul A.N., et al. Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3). Hum Genet 2009, 125:581-590.
4. Hartmann S., Okun J.G., Schmidt C., et al. Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC with electrospray ionization tandem mass spectrometry. Clin Chem 2006, 52:1127-1137.
5. van Kuilenburg A.B., van Lenthe H., Tromp A., Veltman P.C., van Gennip A.H. Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. Clin Chem 2000, 46:9-17.
6. Seck K., Riemer S., Kates R., et al. Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in a cohort of Caucasian individuals. Clin Cancer Res 2005, 11:5886-5892.
7. Brunger A.T. Version 1.2 of the crystallography and NMR system. Nat Protoc 2007, 2:2728-2733.
8. Kleibl Z., Fidlerova J., Kleiblova P., et al. Influence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fluoropyrimidine-related toxicity in patients with high-grade toxicity and patients with excellent tolerance of fluoropyrimidine-based chemotherapy. Neoplasma 2009, 56:303-316.
9. Lohkamp B., Voevodskaya N., Lindqvist Y., Dobritzsch D. Insights into the mechanism of dihydropyrimidine dehydrogenase from site-directed mutagenesis targeting the active site loop and redox cofactor coordination. Biochim Biophys Acta 2010, 1804:2198-2206.
10. Vreken P., van Kuilenburg A.B., Meinsma R., van Gennip A.H. Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet 1997, 101:333-338.
11. van Kuilenburg A.B., Meijer J., Dobritzsch D., et al. Identification of two novel mutations C79X and R235Q in the dihydropyrimidine dehydrogenase gene in a patient presenting with hematuria. Nucleosides Nucleotides Nucleic Acids 2008, 27:809-815.