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

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

Author information

1
Institut Claudius Regaud, IUCT-O, Department of Pharmacology, Toulouse, France.
2
EA4553, Univ. Toulouse III Paul Sabatier, Toulouse, France.
3
UJF Grenoble I, University Hospital Albert Michallon, Department of Pharmacy, Grenoble, France.
4
Institut Daniel Hollard, Department of Medical Oncology, Grenoble, France.
5
University Hospital Albert Michallon, Medical Intensive Care Unit, UJF Grenoble I, Grenoble, France.
6
Centre Oscar Lambret, Department of Medical Oncology, Lille, France.
7
Institut Paoli Calmettes, Department of Medical Oncology, Marseille, France.
8
Institut Claudius Regaud, IUCT-O, Department of Medical Oncology, Toulouse, France.
9
Institut Claudius Regaud, IUCT-O, Laboratory of Oncogenetics, Toulouse, France.

Abstract

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).

PMID:
26265035
DOI:
10.1002/cpt.210
[Indexed for MEDLINE]

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