{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T04:40:00Z","timestamp":1759466400942,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006096","name":"Shiraz Transplant Research Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006096","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"crossref","award":["No.2749"],"award-info":[{"award-number":["No.2749"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Wilson\u2019s disease (WD) is an autosomal recessive disorder characterized by pathological copper accumulation, primarily in the liver and brain. Severe hepatic involvement can be effectively treated with liver transplantation (LT). Geographic variation in ATP7B mutations suggests the presence of regional patterns that may impact disease presentation and management. This study aims to investigate the genetic basis of WD in patients from a major LT center in Iran. Methods: A retrospective analysis was conducted on clinical, biochemical, and pathological data from patients suspected of WD who underwent evaluation for LT between May 2020 and June 2025 at Shiraz University of Medical Sciences. Genetic testing was carried out on 20 patients at the Shiraz Transplant Research Center (STRC). Direct mutation analysis of ATP7B was performed for all patients, and the results correlated with clinical and demographic information. Results: In total, 20 WD patients who underwent liver transplantation (15 males, 5 females) carried 25 pathogenic or likely pathogenic ATP7B variants, 21 of which were previously unreported. Fifteen patients were homozygous, and five were compound-heterozygous; all heterozygous combinations occurred in the offspring of second-degree consanguineous unions. Recurrent changes included p.L549V, p.V872E, and p.P992S\/L, while two nonsense variants (p.E1293X, p.R1319X) predicted truncated proteins. Variants were distributed across copper-binding, transmembrane, phosphorylation, and ATP-binding domains, and in silico AlphaMissense scores indicate damaging effects for most novel substitutions. Post-LT follow-up showed biochemical normalization in the majority of recipients, with five deaths recorded during the study period. Conclusions: This single-center Iranian study reveals a highly heterogeneous ATP7B mutational landscape with a large proportion of novel population-specific variants and underscores the benefit of comprehensive gene sequencing for timely WD diagnosis and family counseling, particularly in regions with prevalent consanguinity.<\/jats:p>","DOI":"10.3390\/diagnostics15192504","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:27:42Z","timestamp":1759328862000},"page":"2504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Characterization of Wilson\u2019s Disease in Liver Transplant Patients: A Five-Year Single-Center Experience in Iran"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-2555","authenticated-orcid":false,"given":"Zahra","family":"Beyzaei","sequence":"first","affiliation":[{"name":"Transplant Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melika","family":"Majed","sequence":"additional","affiliation":[{"name":"Transplant Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Mohsen","family":"Dehghani","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Hadi","family":"Imanieh","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Khazaee","sequence":"additional","affiliation":[{"name":"Transplant Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bita","family":"Geramizadeh","sequence":"additional","affiliation":[{"name":"Transplant Research Center, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"},{"name":"Department of Pathology, Medical School of Shiraz University, Shiraz University of Medical Sciences, Shiraz 7193711351, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC) RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0140-6736(07)60196-2","article-title":"Wilson\u2019s disease","volume":"369","author":"Ala","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ng1293-327","article-title":"The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene","volume":"5","author":"Bull","year":"1993","journal-title":"Nat. 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