{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:35:54Z","timestamp":1790076954276,"version":"4.0.1"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Audiology Research"],"abstract":"<jats:p>The etiology of sensorineural hearing loss is heavily influenced by genetic mutations, with approximately 80% of cases attributed to genetic causes and only 20% to environmental factors. Over 100 non-syndromic deafness genes have been identified in humans thus far. In non-syndromic sensorineural hearing impairment, around 75\u201385% of cases follow an autosomal recessive inheritance pattern. In recent years, groundbreaking advancements in molecular gene therapy for inner-ear disorders have shown promising results. Experimental studies have demonstrated improvements in hearing following a single local injection of adeno-associated virus-derived vectors carrying an additional normal gene or using ribozymes to modify the genome. These pioneering approaches have opened new possibilities for potential therapeutic interventions. Following the PRISMA criteria, we summarized the AAV gene therapy experiments showing hearing improvement in the preclinical phases of development in different animal models of DFNB deafness and the AAV gene therapy programs currently in clinical phases targeting autosomal recessive non syndromic hearing loss. A total of 17 preclinical studies and 3 clinical studies were found and listed. Despite the hurdles, there have been significant breakthroughs in the path of HL gene therapy, holding great potential for providing patients with novel and effective treatment.<\/jats:p>","DOI":"10.3390\/audiolres14020022","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T07:33:56Z","timestamp":1708673636000},"page":"239-253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Autosomal Recessive Non-Syndromic Deafness: Is AAV Gene Therapy a Real Chance?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-4399","authenticated-orcid":false,"given":"Davide","family":"Brotto","sequence":"first","affiliation":[{"name":"Department of Neuroscience DNS, Otolaryngology Section, Padova University, 35128 Padova, Italy"},{"name":"Otolaryngology Unit, Azienda Ospedale Universit\u00e0 Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Greggio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience DNS, Otolaryngology Section, Padova University, 35128 Padova, Italy"},{"name":"Otolaryngology Unit, Azienda Ospedale Universit\u00e0 Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"De Filippis","sequence":"additional","affiliation":[{"name":"Department of Neuroscience DNS, Otolaryngology Section, Padova University, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Trevisi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience DNS, Otolaryngology Section, Padova University, 35128 Padova, Italy"},{"name":"Otolaryngology Unit, Azienda Ospedale Universit\u00e0 Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014A silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1e9","DOI":"10.1016\/j.heares.2011.10.001","article-title":"Deafness in the genomics era","volume":"282","author":"Shearer","year":"2011","journal-title":"Hear. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/coa.12567","article-title":"Features of autosomal recessive nonsyndromic hearing impairment; a review to serve as a reference","volume":"41","author":"Oonk","year":"2016","journal-title":"Clin. Otolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3389\/fncel.2019.00323","article-title":"Gene Therapy for Human Sensorineural Hearing Loss","volume":"13","author":"Ren","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107947","DOI":"10.1016\/j.heares.2020.107947","article-title":"Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges","volume":"394","author":"Askew","year":"2020","journal-title":"Hear Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature25164","article-title":"Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents","volume":"553","author":"Gao","year":"2018","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nbt.3801","article-title":"Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c","volume":"35","author":"Pan","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_8","first-page":"e9396","article-title":"A dual-AAV approach restores fast exocytosis and partially rescues auditory function in deaf otoferlin knock-out mice","volume":"11","author":"Cepeda","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1073\/pnas.1817537116","article-title":"Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model","volume":"116","author":"Akil","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13259","DOI":"10.15252\/emmm.202013259","article-title":"Neonatal AAV gene therapy rescues hearing in a mouse model of SYNE4 deafness","volume":"13","author":"Taiber","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41467-018-08264-w","article-title":"Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders","volume":"10","author":"Pan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/gt.2010.175","article-title":"Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear","volume":"18","author":"Kilpatrick","year":"2011","journal-title":"Gene Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtm.2018.11.003","article-title":"Gene transfer with AAV9-PHP.B rescues hearing in a mouse model of Usher Syndrome 3A and transduces hair cells in a non-human primate","volume":"13","author":"Gyorgy","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107930","DOI":"10.1016\/j.heares.2020.107930","article-title":"Preclinical testing of AAV9-PHP.B for transgene expression in the non-human primate cochlea","volume":"394","author":"Ivanchenko","year":"2020","journal-title":"Hear. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107882","DOI":"10.1016\/j.heares.2020.107882","article-title":"Efficient viral transduction in mouse inner ear hair cells with utricle injection and AAV9-PHP.B","volume":"394","author":"Lee","year":"2020","journal-title":"Hear. Res."},{"key":"ref_16","first-page":"11","article-title":"Delivery of CRISPR\/Cas9 using AAV-PHP.B in the inner ear leads to allele-specific inactivation of the mutated Tmc1 allele and protects auditory function in Beethoven mice","volume":"30","author":"Solanes","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ymthe.2018.12.014","article-title":"Targeted Allele Suppression Prevents Progressive Hearing Loss in the Mature Murine Model of Human TMC1 Deafness","volume":"27","author":"Yoshimura","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e202201592","DOI":"10.26508\/lsa.202201592","article-title":"Mutation-agnostic RNA interference with engineered replacement rescues Tmc1-related hearing loss","volume":"6","author":"Iwasa","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e19763","DOI":"10.1097\/MD.0000000000019763","article-title":"A phase I\/IIa double blind single institute trial of low dose sirolimus for Pendred syndrome\/DFNB4","volume":"99","author":"Fujioka","year":"2020","journal-title":"Medicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.omtm.2021.09.009","article-title":"GJB2 gene therapy and conditional deletion reveal developmental stage-dependent effects on inner ear structure and function","volume":"23","author":"Guo","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/gt.2013.59","article-title":"Virally expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice","volume":"21","author":"Yu","year":"2014","journal-title":"Gene Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/hmg\/ddi172","article-title":"In vitro and in vivo suppression of GJB2 expression by RNA interference","volume":"14","author":"Maeda","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/mt.2015.150","article-title":"Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf Whirler Mice","volume":"24","author":"Chien","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12125","DOI":"10.1038\/s41598-018-29709-8","article-title":"Tmc2 expression partially restores auditory function in a mouse model of DFNB7\/B11 deafness caused by loss of Tmc1 function","volume":"8","author":"Nakanishi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"600051","DOI":"10.3389\/fnmol.2020.600051","article-title":"Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness","volume":"13","author":"Rankovic","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00439-022-02504-2","article-title":"Hearing of Otof-deficient mice restored by trans-splicing of N- and C-terminal otoferlin","volume":"142","author":"Tang","year":"2023","journal-title":"Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1093\/hmg\/ddv109","article-title":"Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness","volume":"24","author":"Iizuka","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1016\/j.ymthe.2023.05.005","article-title":"Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8","volume":"31","author":"Du","year":"2023","journal-title":"Mol Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eabi7629","DOI":"10.1126\/sciadv.abi7629","article-title":"Dual-vector gene therapy restores cochlear amplification and auditory sensitivity in a mouse model of DFNB16 hearing loss","volume":"7","author":"French","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Marcovich, I., Baer, N.K., Shubina-Oleinik, O., Eclov, R., Beard, C.W., and Holt, J.R. (2022). Optimized AAV Vectors for TMC1 Gene Therapy in a Humanized Mouse Model of DFNB7\/11. Biomolecules, 12.","DOI":"10.3390\/biom12070914"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.ymthe.2020.11.016","article-title":"Single and Dual Vector Gene Therapy with AAV9-PHP.B Rescues Hearing in Tmc1 Mutant Mice","volume":"29","author":"Wu","year":"2021","journal-title":"Mol Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"295ra108","DOI":"10.1126\/scitranslmed.aab1996","article-title":"Tmc gene therapy restores auditory function in deaf mice","volume":"7","author":"Askew","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eaay9101","DOI":"10.1126\/scitranslmed.aay9101","article-title":"In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness","volume":"12","author":"Yeh","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1016\/j.ymthe.2023.07.014","article-title":"Combined AAV-mediated gene replacement therapy improves auditory function in a mouse model of human DFNB42 deafness","volume":"31","author":"Isgrig","year":"2023","journal-title":"Mol Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"689415","DOI":"10.3389\/fnmol.2021.689415","article-title":"Cabp2-Gene Therapy Restores Inner Hair Cell Calcium Currents and Improves Hearing in a DFNB93 Mouse Model","volume":"14","author":"Oestreicher","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ymthe.2016.12.010","article-title":"Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV","volume":"25","author":"Sage","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1089\/ars.2015.6442","article-title":"Methionine Sulfoxide Reductase B3-Targeted In Utero Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss","volume":"24","author":"Kim","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_38","unstructured":"(2023, June 12). Gene Therapy Trial for Otoferlin Gene-Mediated Hearing Loss, NCT05821959, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05821959."},{"key":"ref_39","unstructured":"(2023, June 12). A Study of DB-OTO, an AAV Based Gene Therapy, in Children\/Infants with Hearing Loss Due to Otoferlin Mutations (CHORD) NCT05788536, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05788536."},{"key":"ref_40","unstructured":"(2023, June 12). An Investigator Initiated Study for OTOV101N+OTOV101C Injection, NCT05901480, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05901480."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1399-0004.2012.01897.x","article-title":"A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy","volume":"82","author":"Matsunaga","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/cge.12744","article-title":"High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder","volume":"90","author":"Zhang","year":"2016","journal-title":"Clin Genet."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Iwasa, Y., Nishio, S.Y., Yoshimura, H., Kanda, Y., Kumakawa, K., Abe, S., Naito, Y., Nagai, K., and Usami, S. (2013). OTOF mutation screening in Japanese severe to profound recessive hearing loss patients. BMC Med. Genet., 14.","DOI":"10.1186\/1471-2350-14-95"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cell.2006.08.040","article-title":"Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse","volume":"127","author":"Roux","year":"2006","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/7693","article-title":"A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness","volume":"21","author":"Yasunaga","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9933","DOI":"10.1128\/JVI.79.15.9933-9944.2005","article-title":"Packaging capacity of adeno-associated virus serotypes: Impact of larger genomes on infectivity and postentry steps","volume":"79","author":"Grieger","year":"2005","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Blanc, F., Mondain, M., Bemelmans, A.-P., Affortit, C., Puel, J.-L., and Wang, J. (2020). rAAV-Mediated Cochlear Gene Therapy: Prospects and Challenges for Clinical Application. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020589"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Qi, J., Fu, X., Zhang, L., Tan, F., Li, N., Sun, Q., Hu, X., He, Z., Xia, M., and Chai, R. (2022). Current AAV-mediated gene therapy in sensorineural hearing loss. Fundam. Res., in press.","DOI":"10.1016\/j.fmre.2022.08.015"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/00125817-200207000-00004","article-title":"GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review","volume":"4","author":"Kenneson","year":"2002","journal-title":"Genet. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/387080a0","article-title":"Connexin 26 mutations in hereditary nonsyndromic sensorineural deafness","volume":"387","author":"Kelsell","year":"1997","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/MOO.0b013e32830e20b0","article-title":"Gap junctions and connexins in the inner ear: Their roles in homeostasis and deafness","volume":"16","author":"Nickel","year":"2008","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"E34","DOI":"10.1002\/lary.24332","article-title":"GJB2-associated hearing loss: Systematic review of worldwide prevalence, genotype, and auditory phenotype","volume":"124","author":"Chan","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.2741\/4046","article-title":"Autosomal recessive nonsyndromic deafness genes: A review","volume":"17","author":"Duman","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Crispino, G., Di Pasquale, G., Scimemi, P., Rodriguez, L., Galindo Ramirez, F., De Siati, R.D., Santarelli, R.M., Arslan, E., Bortolozzi, M., and Chiorini, J.A. (2011). BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023279"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bbrc.2009.05.023","article-title":"Targeted connexin26 ablation arrests postnatal development of the organ of Corti","volume":"385","author":"Wang","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.2741\/2780","article-title":"TMPRSS3, a type II transmembrane serine protease mutated in non-syndromic autosomal recessive deafness","volume":"13","author":"Guipponi","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1093\/hmg\/11.23.2829","article-title":"The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8\/10 activates the epithelial sodium channel (ENaC) in vitro","volume":"11","author":"Guipponi","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17383","DOI":"10.1074\/jbc.M110.190652","article-title":"Tmprss3, a transmembrane serine protease deficient in human DFNB8\/10 deafness, is critical for cochlear hair cell survival at the onset of hearing","volume":"286","author":"Fasquelle","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/83768","article-title":"Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness","volume":"27","author":"Scott","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"707845","DOI":"10.3389\/fgene.2021.707845","article-title":"Prevalence and Characteristics of STRC Gene Mutations (DFNB16): A Systematic Review and Meta-Analysis","volume":"12","author":"Han","year":"2021","journal-title":"Front. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1038\/s41598-019-40586-7","article-title":"Frequency and clinical features of hearing loss caused by STRC deletions","volume":"9","author":"Yokota","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","article-title":"Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss","volume":"135","author":"Bierer","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e393","DOI":"10.1097\/MAO.0000000000001571","article-title":"STRC deletion is a frequent cause of slight to moderate congenital hearing impairment in the Czech Republic","volume":"38","author":"Plevova","year":"2017","journal-title":"Otol. Neurotol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1097\/MAO.0000000000002059","article-title":"Phenotypic characterization of DFNB16-associated hearing loss","volume":"40","author":"Back","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1007\/s00405-019-05649-5","article-title":"Moderate sensorineural hearing loss is typical for DFNB16 caused by various types of mutations affecting the STRC gene","volume":"276","author":"Cada","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/cge.12332","article-title":"DFNB16 is a frequent cause of congenital hearing impairment: Implementation of STRC mutation analysis in routine diagnostics","volume":"87","author":"Vona","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ng726","article-title":"Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus","volume":"29","author":"Verpy","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jovine, L., Park, J., and Wassarman, P.M. (2002). Sequence similarity between stereocilin and otoancorin points to a unified mechanism for mechanotransduction in the mammalian inner ear. BMC Cell Biol., 3.","DOI":"10.1186\/1471-2121-3-28"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"eaav4523","DOI":"10.1126\/scitranslmed.aav4523","article-title":"Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina","volume":"11","author":"Tornabene","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.neuron.2018.07.033","article-title":"TMC1 Forms the Pore of Mechanosensory Transduction Channels in Vertebrate Inner Ear Hair Cells","volume":"99","author":"Pan","year":"2018","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.neuron.2013.06.019","article-title":"TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear","volume":"79","author":"Pan","year":"2013","journal-title":"Neuron"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ng842","article-title":"Dominant and recessive deafness caused by mutations of a novel gene TMC1 required for cochlear hair-cell function","volume":"30","author":"Kurima","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.anl.2014.04.001","article-title":"Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction","volume":"41","author":"Nakanishi","year":"2014","journal-title":"Auris Nasus Larynx"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10048-016-0477-1","article-title":"Recessive mutations of TMC1 associated with moderate to severe hearing loss","volume":"17","author":"Imtiaz","year":"2016","journal-title":"Neurogenetics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1399-0004.2008.01053.x","article-title":"Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7\/11","volume":"74","author":"Hilgert","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nature01059","article-title":"Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier","volume":"419","author":"Liberman","year":"2002","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"C1213","DOI":"10.1152\/ajpcell.00558.2003","article-title":"The tight junction: A multifunctional complex","volume":"286","author":"Schneeberger","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1083\/jcb.200510043","article-title":"Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells","volume":"171","author":"Ikenouchi","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1242\/jcs.138271","article-title":"Analysis of the \u2018angulin\u2019 proteins LSR, ILDR1 and ILDR2\u2014Tricellulin recruitment, epithelial barrier function and implication in deafness pathogenesis","volume":"126","author":"Higashi","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1242\/jcs.072058","article-title":"LSR defines cell corners for tricellular tight junction formation in epithelial cells","volume":"124","author":"Masuda","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10038-007-0209-3","article-title":"Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families","volume":"53","author":"Chishti","year":"2008","journal-title":"J. Hum. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1086\/510022","article-title":"Tricellulin is a tight-junction protein necessary for hearing","volume":"79","author":"Riazuddin","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/j.1399-0004.2011.01817.x","article-title":"DFNB49 is an important cause of non-syndromic deafness in Czech Roma patients but not in the general Czech population","volume":"82","author":"Lastuvkova","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ajhg.2010.12.011","article-title":"Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42","volume":"88","author":"Borck","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ejmg.2014.04.004","article-title":"ILDR1: Novel mutation and a rare cause of congenital deafness in the Saudi Arabian population","volume":"57","author":"Ramzan","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0074-7696(06)48005-0","article-title":"Tight junctions: Molecular architecture and function","volume":"248","author":"Aijaz","year":"2006","journal-title":"Int. Rev. Cytol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tcb.2009.12.002","article-title":"Dynamics and functions of tight junctions","volume":"20","author":"Steed","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/341397a0","article-title":"How the ear\u2019s works work","volume":"341","author":"Hudspeth","year":"1989","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/j.1399-0004.2010.01593.x","article-title":"DFNB93, a novel locus for autosomal recessive moderate-to-severe hearing impairment","volume":"79","author":"Tabatabaiefar","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E1717","DOI":"10.1073\/pnas.1617533114","article-title":"Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells","volume":"114","author":"Picher","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.heares.2018.04.001","article-title":"Functions of CaBP1 and CaBP2 in the peripheral auditory system","volume":"364","author":"Yang","year":"2018","journal-title":"Hear. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"196","DOI":"10.4274\/balkanmedj.2017.0946","article-title":"A novel variant in SYNE4 confirms its causative role in sensorineural hearing loss","volume":"35","author":"Masterson","year":"2018","journal-title":"Balkan Med. J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1073\/pnas.0808602106","article-title":"Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization","volume":"106","author":"Roux","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.semcdb.2013.12.010","article-title":"Nesprins in health and disease","volume":"29","author":"Cartwright","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_95","first-page":"740","article-title":"The LINC complex is essential for hearing","volume":"123","author":"Horn","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.cell.2012.10.041","article-title":"TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells","volume":"151","author":"Xiong","year":"2012","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ajhg.2010.11.010","article-title":"Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are associated with human deafness DFNB74","volume":"88","author":"Ahmed","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1093\/hmg\/ddt549","article-title":"Methionine sulfoxide reductase B3 deficiency causes hearing loss due to stereocilia degeneration and apoptotic cell death in cochlear hair cells","volume":"23","author":"Kwon","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ymthe.2006.04.003","article-title":"In vivo delivery of recombinant viruses to the fetal murine cochlea: Transduction characteristics and long term effects on auditory function","volume":"14","author":"Bedrosian","year":"2006","journal-title":"Mol. Ther."}],"container-title":["Audiology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4349\/14\/2\/22\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:06Z","timestamp":1760104986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4349\/14\/2\/22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,22]]},"references-count":99,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["audiolres14020022"],"URL":"https:\/\/doi.org\/10.3390\/audiolres14020022","relation":{},"ISSN":["2039-4349"],"issn-type":[{"value":"2039-4349","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,22]]}}}