{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:30:30Z","timestamp":1790029830668,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nature Science Research Project of Jiangxi Province","award":["20232BAB216025"],"award-info":[{"award-number":["20232BAB216025"]}]},{"name":"Jiangxi Province Key Research and Development Project","award":["20232BBG70023"],"award-info":[{"award-number":["20232BBG70023"]}]},{"name":"Jiangxi Province Key Research and Development Project","award":["20202BBG73015"],"award-info":[{"award-number":["20202BBG73015"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260224"],"award-info":[{"award-number":["82260224"]}],"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":["82471183"],"award-info":[{"award-number":["82471183"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20242BAB25491"],"award-info":[{"award-number":["20242BAB25491"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The TECTA gene encodes \u03b1-tectorin, the major non-collagenous glycoprotein of the tectorial membrane, and plays a critical role in intracochlear sound transmission. Unsurprisingly, mutations in TECTA underlie hearing loss in both mice and humans. Two forms of hearing loss are linked to TECTA mutations: DFNA8\/12 (autosomal dominant) and DFNB21 (autosomal recessive). Using a combination of clinical examination, pedigree analysis, exome sequencing, and functional studies, we identified a novel aberrant splicing variant, c.5999G\u2009&amp;gt;\u2009A (p.Gly2000Glu), in TECTA as the cause of autosomal dominant hearing loss in five-generation kindred of Chinese descent and provided prenatal diagnosis for the family. To investigate whether the variant acts via a a dominant-negative effect, consistent with pathogenesis observed in mouse models, we performed in vivo RNA analysis. Our data demonstrated that the variant altered RNA splicing, specifically causing aberrant splicing of exon 20 and resulting in two in-frame deletions. Quantitative real-time polymerase chain reaction revealed no significant reduction in mRNA levels in lymphoblasts derived from individuals harboring the TECTA c.5999G\u2009&amp;gt;\u2009A (p.Gly2000Glu) variant or the TECTA c.5383\u2009+\u20096\u00a0T\u2009&amp;gt;\u2009A splicing variant, previously shown to result in exon 16 skipping. This study confirms the involvement of an aberrant splicing mutation in TECTA in autosomal dominant nonsyndromic hearing loss, expands the mutational landscape of DFNA8\/12 to include coding variants that alter RNA splicing, and underscores the importance of investigating splicing effects of coding variants.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf109","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T03:54:17Z","timestamp":1751255657000},"page":"1517-1525","source":"Crossref","is-referenced-by-count":2,"title":["A novel splicing variant in <i>TECTA<\/i> associated with prelingual autosomal dominant nonsyndromic hearing loss via dominant-negative effect"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1975-8505","authenticated-orcid":false,"given":"Yan","family":"Yang","sequence":"first","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7317-0295","authenticated-orcid":false,"given":"YuanPing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Lai","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxin","family":"Feng","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhongFa","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YaJuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XinYu","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laipeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology , Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, Jiangxi Province 330006, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Luo","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 318, Bayi AvenueDonghu District, Nanchang, Jiangxi Province 330006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhe","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong\u2019an Road, Xicheng District , Beijing 100050 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyi","family":"Zou","sequence":"additional","affiliation":[{"name":"Jiangxi Key Laboratory of Birth Defect Prevention and Control, Jiangxi Maternal and Child Health Hospital , No. 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