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

• DOI: 10.1002/cpt.210
• Publication Date: 2015-08-12T00:46:56Z
• Authors: F Thomas; I Hennebelle; C Delmas; I Lochon; C Dhelens; C Garnier Tixidre; A Bonadona; N Penel; A Goncalves; JP Delord; C Toulas; E Chatelut
• Keywords: DPYD; Dihydropyrimidine dehydrogenase; Uracil

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