{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:45:48Z","timestamp":1791978348781,"version":"4.4.0"},"reference-count":11,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JPGN rep."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thiopurines, such as azathioprine (AZA), are among the immunosuppressants used to prevent allograft rejection. Thiopurines are metabolized by thiopurine S\u2010methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) enzymes, and their functions are highly influenced by genetic variation. We present a 6\u2010year\u2010old female with recurrent acute cellular rejection and steroid\u2010induced glaucoma due to high\u2010dose corticosteroid therapy. Consequently, AZA was incorporated into her calcineurin\u2010inhibitor\u2010based regimen to reduce steroid dose. Within 33 days of initiating AZA, alopecia and pancytopenia developed despite confirmed TPMT enzyme activity with normal phenotype and low 6\u2010Thioguanine and 6\u2010Methylmercaptopurine levels in the blood. Pharmacogenomic analysis revealed an\n                    <jats:italic>NUDT15<\/jats:italic>\n                    *3\/*3 genotype, indicating two \u201cno function\u201d alleles, classified as NUDT15 poor metabolizer at high risk of myelosuppression with standard thiopurine doses. Liver donor pharmacogenomic testing was not performed. This case highlights the consideration of pharmacogenomic testing for recipient and donor prior to thiopurine use in liver\u2010transplant recipients.\n                  <\/jats:p>","DOI":"10.1002\/jpr3.70243","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:53:46Z","timestamp":1791975226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nudix hydrolase 15 deficiency and azathioprine toxicity in a liver transplant recipient: A case report"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7190-1231","authenticated-orcid":false,"given":"Jenny Q.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Personalized Care Program Children's Hospital Los Angeles Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition Children's Hospital Los Angeles Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5471-9083","authenticated-orcid":false,"given":"Kimberly A.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Children's Hospital Los Angeles Los Angeles California USA"},{"name":"Department of Pediatrics Keck School of Medicine of University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-1305","authenticated-orcid":false,"given":"Matthew A.","family":"Deardorff","sequence":"additional","affiliation":[{"name":"Personalized Care Program Children's Hospital Los Angeles Los Angeles California USA"},{"name":"Departments of Pathology and Pediatrics Keck School of Medicine of University of Southern California Los Angeles California USA"},{"name":"Departments of Pathology and Pediatrics Children's Hospital Los Angeles Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-3411","authenticated-orcid":false,"given":"Keith Z.","family":"Hazleton","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition Children's Hospital Los Angeles Los Angeles California USA"},{"name":"Department of Pediatrics Keck School of Medicine of University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/CLD.0000000000000035","article-title":"Brief overview of immunosuppression and its side effects after liver transplantation","volume":"21","author":"Rabiee A","year":"2023","journal-title":"Clin Liver Dis"},{"issue":"4","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/cpt.70209","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2025 update","volume":"119","author":"Maillard M","year":"2026","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_9_4_1","unstructured":"Pharmacogene Variation Consortium (PharmVar). NUDT15 Gene Page (Version 1.7). Published 2026. Accessed May 28 2026.\u00a0https:\/\/www.pharmvar.org\/gene\/NUDT15"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.jmoldx.2022.06.007","article-title":"TPMT and NUDT15 genotyping recommendations: a joint consensus recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase","volume":"24","author":"Pratt VM","year":"2022","journal-title":"J Mol Diagn"},{"key":"e_1_2_9_6_1","unstructured":"Azathioprine Tablets USP: Prescribing Information. Published 2025. Accessed May 28 2026.https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=bc6dc4bd-2121-4613-9d90-4a504010c98a"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1200\/JCO.2014.59.4671","article-title":"Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia","volume":"33","author":"Yang JJ","year":"2015","journal-title":"J Clin Oncol"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/apt.13559","article-title":"Review article: recent advances in pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in inflammatory bowel disease","volume":"43","author":"Moon W","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3390\/metabo14120715","article-title":"A rapid and reliable absorbance assay to identify drug\u2013drug interactions with thiopurine drugs","volume":"14","author":"Russell DA","year":"2024","journal-title":"Metabolites"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cpt.113","article-title":"Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing","volume":"98","author":"Birdwell K","year":"2015","journal-title":"Clin Pharm Ther"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1038\/s41436-019-0448-7","article-title":"Impact of NUDT15 genetics on severe thiopurine\u2010related hematotoxicity in patients with European ancestry","volume":"21","author":"Schaeffeler E","year":"2019","journal-title":"Genet Med"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/MEG.0000000000000564","article-title":"NUDT15 variant is the most common variant associated with thiopurine\u2010induced early leukopenia and alopecia in Korean pediatric patients with Crohn's disease","volume":"28","author":"Lee YJ","year":"2016","journal-title":"Eur J Gastroenterol Hepatol"}],"container-title":["JPGN Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpr3.70243","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jpr3.70243","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpr3.70243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:53:49Z","timestamp":1791975229000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jpr3.70243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":11,"alternative-id":["10.1002\/jpr3.70243"],"URL":"https:\/\/doi.org\/10.1002\/jpr3.70243","archive":["Portico"],"relation":{},"ISSN":["2691-171X","2691-171X"],"issn-type":[{"value":"2691-171X","type":"print"},{"value":"2691-171X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jpr3.70243"}}