{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:10:59Z","timestamp":1791414659522,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T00:00:00Z","timestamp":1447113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p><jats:bold>Despite the growing evidence that dihydropyrimidine dehydrogenase deficiency (DPD, encoded by the <jats:italic>DPYD<\/jats:italic> 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\u2010fluorouracil 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 <jats:italic>DPYD<\/jats:italic> mutations: a novel 8\u2010bp duplication (c.168_175dupGAATAATT, p.Phe59Ter) and c.1679T&gt;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 <jats:italic>DPYD<\/jats:italic> 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 (<jats:italic>P<\/jats:italic> = 0.01)<\/jats:bold>.<\/jats:p>","DOI":"10.1002\/cpt.210","type":"journal-article","created":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T00:46:56Z","timestamp":1439340416000},"page":"235-242","source":"Crossref","is-referenced-by-count":41,"title":["Genotyping of a family with a novel deleterious <i>DPYD<\/i> mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil\/uracil ratio"],"prefix":"10.1111","volume":"99","author":[{"given":"F","family":"Thomas","sequence":"first","affiliation":[{"name":"Institut Claudius Regaud, IUCT\u2010O, Department of Pharmacology Toulouse France"},{"name":"EA4553 Univ. Toulouse III Paul Sabatier Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Hennebelle","sequence":"additional","affiliation":[{"name":"Institut Claudius Regaud, IUCT\u2010O, Department of Pharmacology Toulouse France"},{"name":"EA4553 Univ. Toulouse III Paul Sabatier Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Delmas","sequence":"additional","affiliation":[{"name":"Institut Claudius Regaud, IUCT\u2010O, Department of Pharmacology Toulouse France"},{"name":"EA4553 Univ. Toulouse III Paul Sabatier Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Lochon","sequence":"additional","affiliation":[{"name":"Institut Claudius Regaud, IUCT\u2010O, Department of Pharmacology Toulouse France"},{"name":"EA4553 Univ. Toulouse III Paul Sabatier Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Dhelens","sequence":"additional","affiliation":[{"name":"UJF Grenoble I, University Hospital Albert Michallon, Department of Pharmacy Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Garnier Tixidre","sequence":"additional","affiliation":[{"name":"Institut Daniel Hollard, Department of Medical Oncology Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Bonadona","sequence":"additional","affiliation":[{"name":"University Hospital Albert Michallon, Medical Intensive Care Unit, UJF Grenoble I Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Penel","sequence":"additional","affiliation":[{"name":"Centre Oscar Lambret, Department of Medical Oncology Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Institut Paoli Calmettes, Department of Medical Oncology Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JP","family":"Delord","sequence":"additional","affiliation":[{"name":"EA4553 Univ. Toulouse III Paul Sabatier Toulouse France"},{"name":"Institut Claudius Regaud, IUCT\u2010O, Department of Medical Oncology Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Toulas","sequence":"additional","affiliation":[{"name":"Institut Claudius Regaud, IUCT\u2010O, Laboratory of Oncogenetics Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Chatelut","sequence":"additional","affiliation":[{"name":"Institut Claudius Regaud, IUCT\u2010O, Department of Pharmacology Toulouse France"},{"name":"EA4553 Univ. Toulouse III Paul Sabatier Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.11.3537"},{"key":"e_1_2_8_2_1","first-page":"325","article-title":"Decreased dihydropyrimidine dehydrogenase activity in a population of patients with breast cancer: implication for 5\u2010fluorouracil\u2010based chemotherapy","volume":"4","author":"Lu Z.","year":"1998","journal-title":"Clin. 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