{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T01:27:54Z","timestamp":1786498074401,"version":"build-2736575974"},"posted":{"date-parts":[[2025,8,14]]},"group-title":"Otolaryngology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R01DC020190"],"award-info":[{"award-number":["R01DC020190"]}]},{"name":"NIH","award":["R01DC017166"],"award-info":[{"award-number":["R01DC017166"]}]},{"name":"NIH","award":["R01DC021795"],"award-info":[{"award-number":["R01DC021795"]}]},{"name":"NIH","award":["F31DC021855"],"award-info":[{"award-number":["F31DC021855"]}]},{"name":"NIH","award":["DC000038"],"award-info":[{"award-number":["DC000038"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["VO 2138\/7-1 grant 469177153"],"award-info":[{"award-number":["VO 2138\/7-1 grant 469177153"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["DFG Collaborative Research Center 1690"],"award-info":[{"award-number":["DFG Collaborative Research Center 1690"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"AAO-HNS\/ Deafness Research Foundation"},{"award":["BB\/T016337\/1"],"award-info":[{"award-number":["BB\/T016337\/1"]}],"id":[{"id":"https:\/\/ror.org\/00cwqg982","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020172","name":"RNID","doi-asserted-by":"crossref","award":["Translational Research in Hearing grant (T6)"],"award-info":[{"award-number":["Translational Research in Hearing grant (T6)"]}],"id":[{"id":"10.13039\/501100020172","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Identifying new genes responsible for non-syndromic hearing loss remains a critical goal as many patients still lack a molecular diagnosis despite comprehensive genetic testing. The tectorial membrane (TM) is a specialized acellular matrix of the inner ear, essential for stimulating mechanosensitive hair cell stereocilia bundles and maintaining frequency tuning and auditory sensitivity. Although mutations in genes encoding several non-collagenous proteins found in the TM (TECTA, CEACAM16, OTOG, OTOGL) have been identified as deafness genes, definitive evidence implicating \u03b2-tectorin (TECTB) has been lacking.<\/jats:p>\n                <jats:p>\n                  Here, we present multiple lines of genetic and experimental evidence linking heterozygous missense variants in\n                  <jats:italic>TECTB<\/jats:italic>\n                  (NM_058222.3:c.674G&gt;A, p.Cys225Tyr and NM_058222.3:c.853C&gt;T, p.Arg285Cys), with hearing loss. Each variant affects highly conserved residues within or directly flanking the zona pellucida domain. Using a\n                  <jats:italic>Tectb-C225Y<\/jats:italic>\n                  knock-in mouse model, we show that homozygous animals exhibit severe hearing loss and profound disruption of TM morphology, while heterozygous animals display decreased staining density within the TM and increased susceptibility to noise-induced hearing loss, despite normal auditory thresholds.\n                <\/jats:p>\n                <jats:p>\n                  These findings identify\n                  <jats:italic>TECTB<\/jats:italic>\n                  as a novel human deafness gene, further elucidate its contribution to maintaining TM integrity and resilience against environmentally-related auditory decline.\n                <\/jats:p>","DOI":"10.1101\/2025.08.13.25333146","type":"posted-content","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T17:05:11Z","timestamp":1755191111000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>TECTB<\/i>\n                  Variants Reveal Tectorial Membrane Vulnerability in Dominant Non-Syndromic Hearing Loss"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2781-0412","authenticated-orcid":false,"given":"Evan B.","family":"Hale","sequence":"first","affiliation":[{"name":"Mass Eye and Ear, Eaton Peabody Laboratories, Boston, MA, 02114, USA"},{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, MA, 02115, USA"},{"name":"Speech and Hearing Bioscience and Technology Program, Harvard University, Cambridge, MA, 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-3447","authenticated-orcid":false,"given":"Barbara","family":"Vona","sequence":"additional","affiliation":[{"name":"Institute for Auditory Neuroscience and InnerEarLab, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Auditory Neuroscience and Optogenetics Laboratory, German Primate Center, 37077 G\u00f6ttingen, Germany"},{"name":"Collaborative Research Center 1690 (CRC1690), University of G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Goodyear","sequence":"additional","affiliation":[{"name":"Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0347-9614","authenticated-orcid":false,"given":"Richard T.","family":"Osgood","sequence":"additional","affiliation":[{"name":"Mass Eye and Ear, Eaton Peabody Laboratories, Boston, MA, 02114, USA"},{"name":"Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, MA, 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA, 02115, USA"},{"name":"Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami S.","family":"Amr","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA, 02115, USA"},{"name":"Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA"},{"name":"Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, Cambridge, MA, 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Mojica","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Vivian Pellas Hospital, Managua, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela A. 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