Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W

Human Genetics
P VrekenA H van Gennip

Abstract

Dihydropyrimidine dehydrogenase (DPD) deficiency (McKusick 274270) is an autosomal recessive disease characterized by thymine-uraciluria in homozygous-deficient patients and associated with a variable clinical phenotype. Cancer patients with this defect should not be treated with the usual dose of 5-fluorouracil because of the expected lethal toxicity. In addition, heterozygosity for mutations in the DPD gene increases the risk of toxicity in cancer patients treated with this drug. Sequence analysis in a patient with complete DPD deficiency, previously shown to be heterozygous for the delta C1897 frame-shift mutation, revealed the presence of a novel missense mutation, R235W. Expression of this novel mutation and previously identified missense mutations C29R and R886H in Escherichia coli showed that both C29R and R235W lead to a mutant DPD protein without significant residual enzymatic activity. The R886H mutation, however, resulted in about 25% residual enzymatic activity and is unlikely to be responsible for the DPD-deficient phenotype. We show that the E. coli expression system is a valuable tool for examining DPD enzymatic variants. In addition, two new patients who were both heterozygous for the C29R mutation and the commo...Continue Reading

Citations

Jun 15, 2010·Nucleosides, Nucleotides & Nucleic Acids·A B P van KuilenburgR C M Hennekam
Sep 16, 2005·Anti-cancer Drugs·Myrna CandelariaAlfonso Dueñas-Gonzalez
Mar 17, 2004·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Natália SalgueiroSérgio Castedo
Nov 30, 2006·Current Opinion in Gastroenterology·Irfan M HisamuddinVincent W Yang
May 25, 2006·Clinical Pharmacokinetics·Su-arpa PloylearmsaengAlexander Jetter
Nov 9, 2014·Journal of the National Cancer Institute·Adam M LeeRobert B Diasio
Oct 2, 2007·Comptes rendus biologies·Radhia Ben FredjSaâd Saguem
Mar 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adam M Lee, Robert B Diasio
Aug 21, 2013·Journal of Korean Medical Science·Joong-Gon ShinHyoung Doo Shin
Aug 12, 2014·World Journal of Gastroenterology : WJG·Mariusz Panczyk
Sep 5, 2019·Cancer Chemotherapy and Pharmacology·Vinay SharmaMalkhey Verma
May 10, 2000·Pharmacogenetics·E S Collie-DuguidH L McLeod
Apr 17, 2013·Clinical Pharmacology and Therapeutics·S M OfferR B Diasio
Aug 1, 1998·Journal of Inherited Metabolic Disease·P VrekenA H van Gennip
Oct 28, 2017·Frontiers in Pharmacology·Nurul-Syakima Ab MutalibRahman Jamal
Mar 28, 2019·Frontiers in Oncology·Raffaele PalmirottaFranco Silvestris
Sep 29, 2004·Biochimica Et Biophysica Acta·Klaus D SchnackerzPaul F Cook

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.