{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:11Z","timestamp":1772160071659,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0908201"],"award-info":[{"award-number":["2020YFA0908201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFA0103900"],"award-info":[{"award-number":["2017YFA0103900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870725"],"award-info":[{"award-number":["81870725"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171148"],"award-info":[{"award-number":["82171148"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830029"],"award-info":[{"award-number":["81830029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171141"],"award-info":[{"award-number":["82171141"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000992"],"award-info":[{"award-number":["82000992"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The pathogenic variants in KCNQ4 cause DFNA2 nonsyndromic hearing loss. However, the understanding of genotype\u2013phenotype correlations between KCNQ4 and hearing is limited. Here, we identified a novel KCNQ4 mutation p.G228D from a Chinese family, including heterozygotes characterized by high\u2010frequency hearing loss that is progressive across all frequencies and homozygotes with more severe hearing loss. We constructed a novel murine model with humanized homologous\n                    <jats:italic>Kcnq4<\/jats:italic>\n                    mutation. The heterozygotes had mid\u2010frequency and high\u2010frequency hearing loss at 4\u2009weeks, and moved toward all frequencies hearing loss at 12\u2009weeks, while the homozygotes had severe\u2010to\u2010profound hearing loss at 8\u2009weeks. The degeneration of outer hair cells (OHCs) was observed from basal to apical turn of cochlea. The reduced K\n                    <jats:sup>+<\/jats:sup>\n                    currents and depolarized resting potentials were revealed in OHCs. Remarkably, we observed the loss of inner hair cells (IHCs) in the region corresponding to the frequency above 32\u2009kHz at 8\u201312\u2009weeks. The results suggest the degeneration of OHCs and IHCs may contribute to high\u2010frequency hearing loss in DFNA2 over time. Our findings broaden the variants of KCNQ4 and provide a novel mouse model of progressive hearing loss, which contributes to an understanding of pathogenic mechanism and eventually treatment of DFNA2 progressive hearing loss.\n                  <\/jats:p>","DOI":"10.1111\/cge.14164","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T01:01:16Z","timestamp":1653267676000},"page":"149-154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A humanized murine model, demonstrating dominant progressive hearing loss caused by a novel\n                    <scp>KCNQ4<\/scp>\n                    mutation (p.\n                    <scp>G228D<\/scp>\n                    ) from a large Chinese family"],"prefix":"10.1111","volume":"102","author":[{"given":"Chong","family":"Cui","sequence":"first","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai 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, Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuping","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong Laboratory of Development and Diseases Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Chen","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowei","family":"Huang","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daqi","family":"Wang","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Lv","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuechun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Affiliated Hospital, Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology Shenzhen Bay Laboratory  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luo","family":"Guo","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geng\u2010Lin","family":"Li","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilai","family":"Shu","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine Fudan University  Shanghai China"},{"name":"Institutes of Biomedical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Nantong Laboratory of Development and Diseases Nantong University  Nantong China"},{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co\u2010innovation Center of Neuroregeneration, Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huawei","family":"Li","sequence":"additional","affiliation":[{"name":"ENT institute and Department of Otorhinolaryngology, Eye &amp; 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