{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:32:49Z","timestamp":1793179969030,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fluoropyrimidines are widely used for the treatment of solid tumours, but they carry a significant risk of severe toxicity in patients with dihydropyrimidine dehydrogenase (DPD) deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>\n                      We describe a 50\u2010year\u2010old male with colorectal cancer who received adjuvant XELOX (oxaliplatin and capecitabine) and developed life\u2010threatening grade 3\u20134 toxicities. Routine\n                      <jats:italic>DPYD<\/jats:italic>\n                      genotyping showed no pathogenic variants. Subsequent\n                      <jats:italic>DPYD<\/jats:italic>\n                      exon sequencing identified three heterozygous variants: c.1627A&gt;G, c.2194G&gt;A, and c.2766+3A&gt;T. The latter, a rare intronic variant, was demonstrated to cause exon 21 skipping by mRNA analysis of peripheral blood mononuclear cells (PBMCs). The patient presented a profound DPD deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The c.2766+3A&gt;T variant leads to a non\u2010functional DPD enzyme and is a likely cause of severe fluoropyrimidine\u2010related toxicity. This variant should be considered deleterious.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70782","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:52:59Z","timestamp":1786686779000},"page":"4017-4023","source":"Crossref","is-referenced-by-count":0,"title":["The variant c.2766+3A&gt;T in DPYD leads to exon 21 skipping and is associated with DPD deficiency and severe fluoropyrimidine toxicity"],"prefix":"10.1002","volume":"92","author":[{"given":"Sara","family":"Salvador\u2010Mart\u00edn","sequence":"first","affiliation":[{"name":"Pharmacy Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Taladr\u00edz\u2010Sender","sequence":"additional","affiliation":[{"name":"Pharmacy Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Zapata\u2010Cobo","sequence":"additional","affiliation":[{"name":"Pharmacy Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Hern\u00e1ndez\u2010Osio","sequence":"additional","affiliation":[{"name":"Pharmacy Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Soto\u2010Alsar","sequence":"additional","affiliation":[{"name":"Medical Oncology Service Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-8928","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Revuelta\u2010Herrero","sequence":"additional","affiliation":[{"name":"Pharmacy Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Garc\u00eda\u2010Alfonso","sequence":"additional","affiliation":[{"name":"Medical Oncology Service Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Thomas","sequence":"additional","affiliation":[{"name":"Pharmacology Department Univ. 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