{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:50:17Z","timestamp":1768809017749,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82222016"],"award-info":[{"award-number":["82222016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>KCNQ4<\/jats:italic> is one of the most common disease\u2010causing genes involved in autosomal dominant non\u2010syndromic hearing loss. We previously found that patients with <jats:italic>KCNQ4<\/jats:italic> p.G285S exhibited a much more rapid deterioration in hearing loss than those with other <jats:italic>KCNQ4<\/jats:italic> variants. To determine the rate of hearing loss and assess the disease for further analysis, we performed a long\u2010term follow\u2010up of these patients and generated patient\u2010derived induced pluripotent stem cells (iPSCs), and a mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with <jats:italic>KCNQ4<\/jats:italic> p.G285S from a five\u2010generation family with hearing loss were followed up from 2005 to 2022. iPSCs were generated by stimulating peripheral blood mononuclear cells from the proband, and their pluripotency was determined. The <jats:italic>Kcnq4<\/jats:italic> p.G286S mouse model was generated using CRISPR\/Cas9, and its genotype and phenotype were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) The annual rates of hearing loss at the frequencies of speech were 0.96\u2009dB for the proband and 0.87\u2009dB for his father during the follow\u2010up period, which were faster than patients with other <jats:italic>KCNQ4<\/jats:italic> variants. (2) The patient\u2010derived iPSC line carrying <jats:italic>KCNQ4<\/jats:italic> p.G285S, possessed the capacity of differentiation and pluripotency capacities. (3) Mutant mice with <jats:italic>Kcnq4<\/jats:italic> p.G286S exhibited hearing loss and outer hair cell loss at 1\u2009month of age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with <jats:italic>KCNQ4<\/jats:italic> p.G285S variant exhibited significantly accelerated progression of hearing loss compared to those with other reported variants. Awareness of the natural history of hearing loss associated with <jats:italic>KCNQ4<\/jats:italic> p.G285S is beneficial for genetic counseling and prognosis. The generation of the iPSCs and mouse model can provide a valuable foundation for further in\u2010depth analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>4 <jats:italic>Laryngoscope<\/jats:italic>, 134:2356\u20132363, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.31179","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T12:27:26Z","timestamp":1699964846000},"page":"2356-2363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Natural History of <i>KCNQ4<\/i><scp>p.G285S<\/scp> Related Hearing Loss, Construction of <scp>iPSC<\/scp> and Mouse Model"],"prefix":"10.1002","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6068-3841","authenticated-orcid":false,"given":"Xiaolong","family":"Zhang","sequence":"first","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Shi","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaonan","family":"Wu","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9421-9000","authenticated-orcid":false,"given":"Kaili","family":"Wu","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danyang","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayong","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery The Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA  Beijing 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