{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:55:39Z","timestamp":1791665739490,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2025,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Sensorineural hearing loss (SNHL) is a frequent manifestation of syndromic inherited retinal diseases (IRDs), exemplified by the very rare form of autosomal\u2010dominant Leber congenital amaurosis with early onset deafness (LCAEOD; OMIM #617879). LCAEOD was first described in 2017 in four families segregating heterozygous missense mutations in\n TUBB4B<\/jats:italic>\n , a gene encoding a \u03b2\u2010tubulin isotype. To date, only eight more families with similar\n TUBB4B<\/jats:italic>\n \u2010associated sensorineural disease (SND) have been reported. Most cases harbored missense variants affecting the same amino acid (Arg391) and only three families segregated variants involving different residues (Tyr310, Arg390).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We performed whole\u2010exome sequencing and a full ophthalmological and audiological examination of the affected members in an Italian family segregating syndromic IRD with early onset deafness.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified a novel, ultra\u2010rare, disease\u2010causing variant in\n TUBB4B<\/jats:italic>\n (NM_006088.6:c.1049A>C) that replaces a highly conserved lysine with threonine at amino acid position 350. The functional impact of the Lys350Thr substitution was supported by protein structure modeling studies. The variant segregates in the family members presenting retinal disease with early onset SNHL. Detailed ophthalmological assessment of the affected subjects diagnosed a progressive cone\u2010rod dystrophy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings expand the limited number of disease\u2010causing\n TUBB4B<\/jats:italic>\n variants, corroborating their association with SND forms, and suggest Lys350 is an important residue for \u03b2\u2010tubulin function. Interestingly, our results demonstrate that\n TUBB4B<\/jats:italic>\n mutations can cause cone\u2010dominated retinal phenotypes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70068","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T04:21:29Z","timestamp":1738124489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Variant in\n \n TUBB4B<\/i>\n <\/scp>\n Causes Progressive Cone\u2010Rod Dystrophy and Early Onset Sensorineural Hearing Loss"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7367-7911","authenticated-orcid":false,"given":"Margherita","family":"Scarpato","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Precision Medicine University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1482-1577","authenticated-orcid":false,"given":"Francesco","family":"Testa","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nesti","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Zeuli","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Precision Medicine University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Boccia","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Auletta","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive Science and Dentistry University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Banfi","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Precision Medicine University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine Pozzuoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Simonelli","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0757-3330","authenticated-orcid":false,"given":"Marianthi","family":"Karali","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Precision Medicine University of Campania \u2018Luigi Vanvitelli\u2019 Naples Italy"},{"name":"Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic University of Campania \u2018Luigi Vanvitelli\u2019 Naples 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