{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:29:38Z","timestamp":1755221378773,"version":"3.43.0"},"reference-count":18,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Health of the Basque Government","award":["2019111052"],"award-info":[{"award-number":["2019111052"]}]},{"name":"Department of Education of the Basque Government","award":["IT-1281-19"],"award-info":[{"award-number":["IT-1281-19"]}]},{"name":"Instituto de Salud Carlos III and co-funded by European Union","award":["PI21\/01419"],"award-info":[{"award-number":["PI21\/01419"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Somatic variants in the <jats:italic>ZFX<\/jats:italic> gene have been found in human sporadic parathyroid adenomas. This gene encodes a transcriptional factor recently described as a transcriptional activator in multiple types of human tumors. We present the clinical and molecular characterization of three patients diagnosed with primary hyperparathyroidism (PHPT) who have germline variants in the <jats:italic>ZFX<\/jats:italic> gene. The first patient had a pathogenic missense variant (c.2321A\u2009&gt;\u2009G; p.(Tyr774Cys)) in the heterozygous state. This patient exhibited PHPT along with ear, nose and forehead abnormalities. Additionally, she presented other characteristics seen in patients with pathogenic variants in the <jats:italic>ZFX<\/jats:italic> gene, such as hearing loss and multiple cutaneous nevi. The second and third patients had a missense variant of uncertain significance (c.1606C\u2009&gt;\u2009T; p.(Arg536Cys)) and an in-frame insertion (c.452_460dup; p.(Gly151_Val153dup)) of uncertain significance, respectively, both in the heterozygous state. These patients had no hearing loss, cutaneous melanocytic nevi, or bone or facial deformities. <jats:italic>ZFX<\/jats:italic> may be one of the genes to be analyzed in women affected by PHPT with suspected genetic inheritance, especially if they have other features such as facial deformities, hearing loss, and cutaneous melanocytic nevi.<\/jats:p>","DOI":"10.1371\/journal.pone.0329388","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T17:28:26Z","timestamp":1754674106000},"page":"e0329388","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of germline variants in the ZFX gene with primary hyperparathyroidism"],"prefix":"10.1371","volume":"20","author":[{"given":"Ainhoa Camille","family":"Aranaga-Decori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-796X","authenticated-orcid":true,"given":"Pedro","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"G\u00f3mez-Conde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leire","family":"Madariaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Valdes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-6600","authenticated-orcid":true,"given":"Alejandro","family":"Garc\u00eda-Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Calcium and Phosphorus Metabolism Molecular Biology Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"issue":"25","key":"pone.0329388.ref001","article-title":"Primary Hyperparathyroidism","volume":"379","year":"2018","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0329388.ref002","doi-asserted-by":"crossref","first-page":"60","DOI":"10.11138\/ccmbm\/2017.14.1.060","article-title":"Molecular genetics in primary hyperparathyroidism: the role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning. A 2017 update","volume":"14","author":"F Marini","year":"2017","journal-title":"Clin Cases Miner Bone Metab"},{"issue":"1","key":"pone.0329388.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18632\/oncoscience.116","article-title":"Erratum: Recurrent ZFX mutations in human sporadic parathyroid adenomas","volume":"2","author":"C-P Soong","year":"2014","journal-title":"Oncoscience"},{"issue":"1","key":"pone.0329388.ref004","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0888-7543(90)90516-W","article-title":"Chromosomal localization of ZFX--a human gene that escapes X inactivation--and its murine homologs","volume":"7","author":"DC Page","year":"1990","journal-title":"Genomics"},{"issue":"7","key":"pone.0329388.ref005","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/0092-8674(89)90061-5","article-title":"ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation","volume":"57","author":"A Schneider-G\u00e4dicke","year":"1989","journal-title":"Cell"},{"issue":"11","key":"pone.0329388.ref006","doi-asserted-by":"crossref","first-page":"5986","DOI":"10.1093\/nar\/gkaa384","article-title":"Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters","volume":"48","author":"W Ni","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0329388.ref007","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1101\/gr.228809.117","article-title":"ZFX acts as a transcriptional activator in multiple types of human tumors by binding downstream from transcription start sites at the majority of CpG island promoters","volume":"28","author":"SK Rhie","year":"2018","journal-title":"Genome Res"},{"issue":"2","key":"pone.0329388.ref008","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cell.2007.03.014","article-title":"Zfx controls the self-renewal of embryonic and hematopoietic stem 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H1299","volume":"6","author":"K Li","year":"2013","journal-title":"Int J Clin Exp Pathol"},{"issue":"3","key":"pone.0329388.ref012","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ajhg.2024.01.007","article-title":"Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt","volume":"111","author":"JL Shepherdson","year":"2024","journal-title":"Am J Hum Genet"},{"issue":"5","key":"pone.0329388.ref013","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"issue":"7","key":"pone.0329388.ref014","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1210\/clinem\/dgad002","article-title":"Genomic Profiling Reveals the Variant Landscape of Sporadic Parathyroid Adenomas in Chinese Population","volume":"108","author":"X Tao","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"pone.0329388.ref015","doi-asserted-by":"crossref","first-page":"631680","DOI":"10.3389\/fendo.2021.631680","article-title":"Integrated Whole-Exome and Transcriptome Sequencing of Sporadic Parathyroid Adenoma","volume":"12","author":"Y Hu","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"8","key":"pone.0329388.ref016","article-title":"A Germline ZFX Missense Variant in a Patient With Primary Hyperparathyroidism","volume":"2","author":"B Guan","year":"2024","journal-title":"JCEM Case Rep"},{"issue":"8","key":"pone.0329388.ref017","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1016\/j.ajhg.2022.06.007","article-title":"Large-scale analyses of the X chromosome in 2,354 infertile men discover recurrently affected genes associated with spermatogenic 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