{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:47:47Z","timestamp":1791229667735,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011541","name":"Division of Cancer Epidemiology and Genetics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n PARN<\/jats:italic>\n encodes poly(A)\u2010specific ribonuclease, a 3 exoribonuclease important in regulating RNA stability and maturation. Rare germline\n PARN<\/jats:italic>\n variants have been reported in telomere biology disorders (TBDs) leading to its inclusion on gene panels for bone marrow failure syndromes and pulmonary diseases.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To understand the extent of germline\n PARN<\/jats:italic>\n variation in human disease, we conducted a comprehensive literature review, curated the TBD\u2010associated\n PARN<\/jats:italic>\n variants using AutoGVP and\n in silico<\/jats:italic>\n prediction tools (MetaSVM, REVEL, and\/or CADD) and assessed their frequency in the gnomAD database.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Ninety\u2010three unique\n PARN<\/jats:italic>\n variants were identified in the literature as present in individuals or families affected by TBDs, but clinical features were not consistently reported. Forty\u2010one variants (44.1%) were classified as pathogenic or likely pathogenic. These variants were spread across the entire gene with no obvious clustering. gnomAD data were notable for a paucity of common variants and metrics suggesting\n PARN<\/jats:italic>\n variation would be tolerated.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The extent to which specific\n PARN<\/jats:italic>\n variants can be associated with TBD etiology is limited due to incomplete literature, clinical data, lack of robust functional assays, and high frequency of rare variants.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70107","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:35:51Z","timestamp":1748496951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Germline\n PARN<\/i>\n Variants in Telomere Biology Disorders and Challenges in Variant Curation"],"prefix":"10.1002","volume":"13","author":[{"given":"Hasset T.","family":"Nurelegne","sequence":"first","affiliation":[{"name":"Clinical Genetics Branch, Division of Cancer and Epidemiology and Genetics, National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mone't B.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Clinical Genetics Branch, Division of Cancer and Epidemiology and Genetics, National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin C.","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Clinical Genetics Branch, Division of Cancer and Epidemiology and Genetics, National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley S.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Clinical Genetics Branch, Division 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