{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:06Z","timestamp":1753869726407,"version":"3.41.2"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>POU4F3<\/jats:italic> mutations cause DFNA15, an autosomal dominant nonsyndromic hearing loss. POU4F3 encodes a transcription factor crucial for inner ear hair cell development and maintenance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify and functionally characterize novel <jats:italic>POU4F3<\/jats:italic> mutations in two Chinese families with late\u2010onset progressive hearing loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Massively parallel DNA sequencing (MPS) was performed on affected individuals from two unrelated Chinese families. Sanger sequencing validated mutations and confirmed co\u2010segregation. Functional analyses included protein expression analysis by Western blots and subcellular localization studies by immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified two novel nonsense mutations in <jats:italic>POU4F3<\/jats:italic>: c.863C\u2009&gt;\u2009A (p.Ser288Ter) and c.172G\u2009&gt;\u2009T (p.Glu58Ter), both co\u2010segregating with the hearing loss phenotype. Functional studies showed p.Ser288Ter produced a stable but mislocalized protein with impaired nuclear transport, while p.Glu58Ter resulted in a severely truncated, rapidly degraded protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study expands the DFNA15 mutation spectrum and provides new insights into POU4F3\u2010related hearing loss pathogenesis. Our findings demonstrate that different molecular mechanisms can lead to similar DFNA15 phenotypes, supporting POU4F3 haploinsufficiency as the primary pathogenic mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70100","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T07:59:46Z","timestamp":1747209586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Correlation of Two Novel Nonsense <scp><i>POU4F3<\/i><\/scp> Mutations Causing Late\u2010Onset Progressive Nonsyndromic Hearing Loss in <scp>DFNA15<\/scp> Families"],"prefix":"10.1002","volume":"13","author":[{"given":"Tianyang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery Xinhua Hospital, Shanghai Jiaotong University School of Medicine  Shanghai China"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Qidong People's Hospital, Qidong Liver Cancer Institute Affiliated Qidong Hospital of Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-081X","authenticated-orcid":false,"given":"Luping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingchun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery Xinhua Hospital, Shanghai Jiaotong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy158"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.21.285643"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20693"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/381603a0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109568.2007.05332.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh218"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.04.132"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201038272\u2010w"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20763"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050700"},{"key":"e_1_2_9_12_1","unstructured":"Shearer A. E. M. S.Hildebrand A. M.Odell andR. J.Smith.2023.\u201cHereditary Hearing Loss and Deafness Overview.\u201d In GeneReviews: University of Washington Seattle."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000058308"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5358.1950"},{"key":"e_1_2_9_15_1","unstructured":"Walls W. D. H.Azaiez andR. J. H.Smith.2024.\u201cHereditary Hearing Loss Homepage.\u201dhttps:\/\/hereditaryhearingloss.org."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.22.7957\u20107964.2003"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1177"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.17.9445"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-024-00628-2"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009040"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T07:33:03Z","timestamp":1748071983000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/mgg3.70100"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70100","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70100"}}