Genotyping of a family with a novel deleterious DPYD mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil/uracil ratio

Clin Pharmacol Ther. 2016 Feb;99(2):235-42. doi: 10.1002/cpt.210. Epub 2015 Nov 10.


Despite the growing evidence that dihydropyrimidine dehydrogenase deficiency (DPD, encoded by the DPYD gene) confers a higher risk of developing severe toxicity, most patients are not screened for DPD deficiency before fluoropyrimidine treatment. We report here the genetic and phenotypic analyses of DPD in a family related to a patient who died after a first cycle of 5-fluorouracil and in 15 additional retrospective patients having a partial DPD deficiency (as measured by plasma dihydrouracil/uracil ratio). The patient with lethal toxicity was found to be a compound heterozygote for two DPYD mutations: a novel 8-bp duplication (c.168_175dupGAATAATT, p.Phe59Ter) and c.1679T>G (Ile560Ser). The patient's dihydrouracil/uracil ratio indicates complete DPD deficiency. The novel mutation was found in two members of the patient's family. Deleterious DPYD mutations were identified in 9 out of the 15 patients. The relationship between genotype and dihydrouracil/uracil values in the 22 patients of the present study was significant (P = 0.01).

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / adverse effects
  • Biotransformation
  • DNA / genetics*
  • Dihydropyrimidine Dehydrogenase Deficiency / diagnosis*
  • Dihydropyrimidine Dehydrogenase Deficiency / genetics*
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Family
  • Fatal Outcome
  • Female
  • Fluorouracil / adverse effects
  • Gene Duplication
  • Genetic Variation
  • Genotype*
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Retrospective Studies
  • Uracil / analogs & derivatives*
  • Uracil / metabolism


  • Antimetabolites, Antineoplastic
  • dihydrouracil
  • Uracil
  • DNA
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil