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In this study, by using a next\u2010generation sequencing panel targeting 127 deafness genes, we identified a pathogenic frameshift mutation c.704_705del and a missense mutation c.593G&gt;A in two three\u2010generation Chinese families with late\u2010onset progressive ADNSHL, respectively. The novel mutations of <jats:italic>POU4F3<\/jats:italic> co\u2010segregated with the deafness phenotype in these two families. c.704_705del caused a frameshift p.T235fs and c.593G&gt;A caused an amino acid substitution of p.R198H. Both mutations led to an abnormal and incomplete protein structure. <jats:italic>POU4F3<\/jats:italic> with either of the two mutations was transiently transfected into HEI\u2010OC1 and HEK 293 cell lines and immunofluorescence assay was performed to investigate the subcellular localization of mutated protein. The results indicated that both c.704_705del (p.T235fs) and c.593G&gt;A (p.R198H) could impair the nuclear localization function of POU4F3. The p.R198H POU4F3 protein was detected as a weak band of the correct molecular weight, indicating that the stability of p.R198H POU4F3 differed from that of the wild\u2010type protein. While, the p.T235fs POU4F3 protein was expressed with a smaller molecular weight, implying this mutation result in a frameshift and premature termination of the POU4F3 protein. In summary, we report two novel mutations of <jats:italic>POU4F3<\/jats:italic> associated with progressive ADNSHL and explored their effects on POU4F3 nuclear localization. These findings expanded the mutation spectrum of <jats:italic>POU4F3<\/jats:italic> and provided new knowledge for the pathogenesis of <jats:italic>POU4F3<\/jats:italic> in hearing loss.<\/jats:p>","DOI":"10.1111\/jcmm.15359","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T07:48:47Z","timestamp":1589183327000},"page":"6978-6987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of two novel mutations in POU4F3 gene associated with autosomal dominant hearing loss in Chinese families"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4027-7798","authenticated-orcid":false,"given":"Xiaohui","family":"Bai","sequence":"first","affiliation":[{"name":"Otologic Center Shandong Provincial ENT Hospital, Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Department of Clinical Laboratory Shandong Provincial Hospital, 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Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Otologic Center Shandong Provincial ENT Hospital, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Otologic Center Shandong Provincial ENT Hospital, Cheeloo College of Medicine Shandong University Jinan 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