{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:44Z","timestamp":1787027684456,"version":"build-2736575974"},"reference-count":80,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Pathogenic missense variants in COCH are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic COCH variant. The literature search yielded 48 studies describing the audiovestibular phenotypes of 27 DFNA9-associated variants in COCH. Subsequently, meta-analysis of audiometric data was performed by constructing age-related typical audiograms and by performing non-linear regression analyses on the age of onset and progression of hearing loss. Significant differences were found between the calculated ages of onset and progression of the audiovestibular phenotypes of subjects with pathogenic variants affecting either the LCCL domain of cochlin or the vWFA2 and Ivd1 domains. We conclude that the audiovestibular phenotypes associated with DFNA9 are highly variable. Variants affecting the LCCL domain of cochlin generally lead to more progression of hearing loss when compared to variants affecting the other domains. This review serves as a reference for prospective natural history studies in anticipation of mutation-specific therapeutic interventions.<\/jats:p>","DOI":"10.3390\/biom12020220","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T21:59:55Z","timestamp":1643320795000},"page":"220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genotype-Phenotype Correlations of Pathogenic COCH Variants in DFNA9: A HuGE Systematic Review and Audiometric Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5082-0005","authenticated-orcid":false,"given":"Sybren M. M.","family":"Robijn","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J.","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"},{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadriye","family":"Sezer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L. M.","family":"Huygen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-6113","authenticated-orcid":false,"given":"Andy J.","family":"Beynon","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-3460","authenticated-orcid":false,"given":"Erwin","family":"van Wijk","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-8693","authenticated-orcid":false,"given":"Hannie","family":"Kremer","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"},{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-3269","authenticated-orcid":false,"given":"Erik","family":"de Vrieze","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-7766","authenticated-orcid":false,"given":"Cornelis P.","family":"Lanting","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5517-9683","authenticated-orcid":false,"given":"Ronald J. E.","family":"Pennings","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hearing & Genes, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6500 GL Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, February 01). Deafness and Hearing Loss, Available online: http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/deafness-and-hearing-loss."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/lio2.134","article-title":"Age-related hearing loss: Unraveling the pieces","volume":"3","author":"Tu","year":"2018","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.heares.2012.12.015","article-title":"Progressive hereditary hearing impairment caused by a MYO6 mutation resembles presbyacusis","volume":"299","author":"Oonk","year":"2013","journal-title":"Hear. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1001\/archotol.134.3.294","article-title":"Audiometric characteristics of a Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3","volume":"134","author":"Pauw","year":"2008","journal-title":"Arch. Otolaryng Head Neck Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/hmg\/5.6.853","article-title":"A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6","volume":"5","author":"Marietta","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/jmedgenet-2020-106863","article-title":"A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss","volume":"58","author":"Smits","year":"2021","journal-title":"J. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41431-017-0066-2","article-title":"Bi-allelic inactivating variants in the COCH gene cause autosomal recessive prelingual hearing impairment","volume":"26","author":"JanssensdeVarebeke","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/humu.22701","article-title":"Identification of Pathogenic Mechanisms of COCH Mutations, Abolished Cochlin Secretion, and Intracellular Aggregate Formation: Genotype-Phenotype Correlations in DFNA9 Deafness and Vestibular Disorder","volume":"35","author":"Bae","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/3118","article-title":"Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction","volume":"20","author":"Robertson","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1097\/00129492-200109000-00009","article-title":"COCH5B2 is a target antigen of anti-inner ear antibodies in autoimmune inner ear diseases","volume":"22","author":"Boulassel","year":"2001","journal-title":"Otol. Neurotol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.chom.2019.02.001","article-title":"Cleaved Cochlin Sequesters Pseudomonas aeruginosa and Activates Innate Immunity in the Inner Ear","volume":"25","author":"Jung","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"449","DOI":"10.5483\/BMBRep.2020.53.9.104","article-title":"Cochlin-cleaved LCCL is a dual-armed regulator of the innate immune response in the cochlea during inflammation","volume":"53","author":"Rhyu","year":"2020","journal-title":"BMB Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108162","DOI":"10.1016\/j.heares.2020.108162","article-title":"On the pathophysiology of DFNA9: Effect of pathogenic variants in the COCH gene on inner ear functioning in human and transgenic mice","volume":"401","author":"Verdoodt","year":"2021","journal-title":"Hear. Res."},{"key":"ref_14","unstructured":"Cochrane Reviews, Higgins, J., and Green, S. (2011). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, The Cochrane Collaboration. Available online: https:\/\/handbook-5-1.cochrane.org\/."},{"key":"ref_15","unstructured":"University of York: Centre for Reviews and Dissemination (2019, June 02). Chapters 1-6. CRD\u2019s Guidance for Undertaking Reviews in Health Care. Available online: https:\/\/www.york.ac.uk\/media\/crd\/Systematic_Reviews.pdf."},{"key":"ref_16","unstructured":"Little, J., and Higgins, J. (2006). The HuGENet\u2122 HuGE Review Handbook, Version 1.0, Centers for Disease Control and Prevention."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"151","author":"Moher","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1097\/00005537-199909000-00031","article-title":"Progressive cochleovestibular impairment caused by a point mutation in the COCH gene at DFNA9","volume":"109","author":"Bom","year":"1999","journal-title":"Laryngoscope"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/hmg\/8.2.361","article-title":"A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects","volume":"8","author":"Bom","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/000348940311200316","article-title":"Cross-sectional analysis of hearing threshold in relation to age in a large family with cochleovestibular impairment thoroughly genotyped for DFNA9\/COCH","volume":"112","author":"Bom","year":"2003","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1001\/archotol.127.9.1045","article-title":"Speech recognition scores related to age and degree of hearing impairment in DFNA2\/KCNQ4 and DFNA9\/COCH","volume":"127","author":"Bom","year":"2001","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1097\/01.mao.0000185048.84641.e3","article-title":"Vestibular deterioration precedes hearing deterioration in the P51SCOCH mutation (DFNA9): An analysis in 74 mutation carriers","volume":"26","author":"Bischoff","year":"2005","journal-title":"Otol. Neurotol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1046\/j.1365-2273.2001.00505.x","article-title":"Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): A follow-up study of a family","volume":"26","author":"Verhagen","year":"2001","journal-title":"Clin. Otolaryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1152\/jn.00082.2017","article-title":"Bayesian quantification of sensory reweighting in a familial bilateral vestibular disorder (DFNA9)","volume":"119","author":"Alberts","year":"2018","journal-title":"J. Neurophysiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/ajmg.a.31354","article-title":"Identification of a novel COCH mutation, G87W, causing autosomal dominant hearing impairment (DFNA9)","volume":"140A","author":"Collin","year":"2006","journal-title":"Am. J. Med. Genet. A."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/000348940711600506","article-title":"Phenotype description of a novel DFNA9\/COCH mutation, I109T","volume":"116","author":"Pauw","year":"2007","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e399","DOI":"10.1097\/MAO.0000000000003004","article-title":"A Novel COCH Mutation Affects the vWFA2 Domain and Leads to a Relatively Mild DFNA9 Phenotype","volume":"42","author":"Smits","year":"2021","journal-title":"Otol. Neurotol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/16513860310003049","article-title":"Characterizing and distinguishing progressive phenotypes in nonsyndromic autosomal dominant hearing impairment","volume":"1","author":"Huygen","year":"2003","journal-title":"Audiol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1177\/000348941112000612","article-title":"Phenotype analysis of an Australian DFNA9 family with the 1109N COCH mutation","volume":"120","author":"Pauw","year":"2011","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1007\/s00405-015-3885-1","article-title":"Distinct vestibular phenotypes in DFNA9 families with COCH variants","volume":"273","author":"Kim","year":"2016","journal-title":"Eur. Arch. Oto-Rhino-Laryn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1002\/lary.21159","article-title":"A Novel Mutation in COCH-Implications for Genotype-Phenotype Correlations in DFNA9 Hearing Loss","volume":"120","author":"Hildebrand","year":"2010","journal-title":"Laryngoscope"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.ijporl.2013.07.031","article-title":"Clinical characterization of a novel COCH mutation G87V in a Chinese DFNA9 family","volume":"77","author":"Chen","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/hmg\/8.8.1425","article-title":"High prevalence of symptoms of Meniere\u2019s disease in three families with a mutation in the COCH gene","volume":"8","author":"Fransen","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1097\/MAO.0000000000000283","article-title":"Focal Sclerosis of Semicircular Canals With Severe DFNA9 Hearing Impairment Caused by a P51S COCH-Mutation: Is There a Link?","volume":"35","author":"Termote","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1001\/archneur.57.7.1045","article-title":"Familial progressive vestibulocochlear dysfunction caused by a COCH mutation (DFNA9)","volume":"57","author":"Verhagen","year":"2000","journal-title":"Arch. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1097\/01.mao.0000185062.12458.87","article-title":"Audiometric, vestibular, and genetic aspects of a DFNA9 family with a G88E COCH mutation","volume":"26","author":"Kemperman","year":"2005","journal-title":"Otol. Neurotol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1097\/00129492-200111000-00028","article-title":"Hereditary otovestibular dysfunction and Meniere\u2019s disease in a large Belgian family is caused by a missense mutation in the COCH gene","volume":"22","author":"Verstreken","year":"2001","journal-title":"Otol. Neurotol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/sj.ejhg.5201043","article-title":"Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere\u2019s disease","volume":"11","author":"Usami","year":"2003","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1097\/00129492-200309000-00009","article-title":"Progressive late-onset sensorineural hearing loss and vestibular impairment with vertigo (DFNA9\/COCH): Longitudinal analyses in a Belgian family","volume":"24","author":"Lemaire","year":"2003","journal-title":"Otol. Neurotol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1399-0004.2009.01362.x","article-title":"The Trp117Arg mutation of the COCH gene causes deafness in Koreans","volume":"77","author":"Baek","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1399-0004.2008.00972.x","article-title":"Novel mutations in the vWFA2 domain of COCH in two Chinese DFNA9 families","volume":"73","author":"Yuan","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/humu.37","article-title":"Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families","volume":"17","author":"Kamarinos","year":"2001","journal-title":"Hum. Mutat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/ajmg.a.32618","article-title":"Mutation in the COCH Gene Is Associated With Superior Semicircular Canal Dehiscence","volume":"149A","author":"Hildebrand","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1136\/jmg.2003.012286","article-title":"A novel COCH mutation, V104del, impairs folding of the LCCL domain of cochlin and causes progressive hearing loss","volume":"41","author":"Nagy","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.amjoto.2012.11.002","article-title":"Novel COCH mutation in a family with autosomal dominant late onset sensorineural hearing impairment and tinnitus","volume":"34","author":"Gallant","year":"2013","journal-title":"Am. J. Otolaryngol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100S","DOI":"10.1177\/0003489415573074","article-title":"Detailed Hearing and Vestibular Profiles in the Patients with COCH Mutations","volume":"124","author":"Tsukada","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/ajmg.a.30980","article-title":"A novel DFNA9 mutation in the vWFA2 domain of COCH alters a conserved cysteine residue and intrachain disulfide bond formation resulting in progressive hearing loss and site-specific vestibular and central oculomotor dysfunction","volume":"139A","author":"Street","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000097794","article-title":"Clinical characteristics of a Dutch DFNA9 family with a novel COCH mutation, G87W","volume":"12","author":"Pauw","year":"2007","journal-title":"Audiol. Neuro-Otol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/1651386X.2010.538523","article-title":"A novel mutation in the vWFA2 domain of the COCH gene in an Italian DFNA9 family","volume":"9","author":"Faletra","year":"2011","journal-title":"Audiol. Med."},{"key":"ref_50","unstructured":"McComiskey, D.A. (2010). Investigation of the Genetic Cause of Hearing Loss in 28 Autosomal Dominant Families within the Newfoundland Founder Population. [Master\u2019s Thesis, Memorial University of Newfoundland]."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31","DOI":"10.17430\/1002738","article-title":"Postlingual sensorineural hearing loss due to a very rare coch pathogenic variant","volume":"8","author":"Tacikowska","year":"2018","journal-title":"J. Hear. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wang, Q., Fei, P., Gu, H., Zhang, Y., Ke, X., and Liu, Y. (2017). Different phenotypes of the two Chinese probands with the same c.889G>A (p.C162Y) mutation in COCH gene verify different mechanisms underlying autosomal dominant nonsyndromic deafness 9. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170011"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1007\/s12105-019-01073-7","article-title":"First Report of Bilateral External Auditory Canal Cochlin Aggregates (\u201cCochlinomas\u201d) with Multifocal Amyloid-Like Deposits, Associated with Sensorineural Hearing Loss and a Novel Genetic Variant in COCH Encoding Cochlin","volume":"14","author":"Basu","year":"2020","journal-title":"Head Neck Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00508-017-1230-y","article-title":"Identification of a rare COCH mutation by whole-exome sequencing Implications for personalized therapeutic rehabilitation in an Austrian family with non-syndromic autosomal dominant late-onset hearing loss","volume":"130","author":"Parzefall","year":"2018","journal-title":"Wien. Klin. Wochen."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5310192","DOI":"10.1155\/2016\/5310192","article-title":"Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH","volume":"2016","author":"Gu","year":"2016","journal-title":"Neural. Plast."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1097\/00005537-200008000-00030","article-title":"DFNA9 is a progressive audiovestibular dysfunction with a microfibrillar deposit in the inner ear","volume":"110","author":"Khetarpal","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1097\/MAO.0000000000000747","article-title":"Targeted Exome Sequencing of Deafness Genes After Failure of Auditory Phenotype-Driven Candidate Gene Screening","volume":"36","author":"Kim","year":"2015","journal-title":"Otol. Neurotol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1159\/000443822","article-title":"Histopathology of the Human Inner Ear in the p.L114P COCH Mutation (DFNA9)","volume":"21","author":"Burgess","year":"2016","journal-title":"Audiol. Neuro-Otol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"45","DOI":"10.7874\/kja.2014.18.2.45","article-title":"Strategy for the customized mass screening of genetic sensorineural hearing loss in koreans","volume":"18","author":"Chang","year":"2014","journal-title":"Korean J. Audiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12967-014-0311-1","article-title":"Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss","volume":"12","author":"Wei","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Choi, B.Y., Park, G., Gim, J., Kim, A.R., Kim, B.J., Kim, H.S., Park, J.H., Park, T., Oh, S.H., and Han, K.H. (2013). Diagnostic Application of Targeted Resequencing for Familial Nonsyndromic Hearing Loss. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068692"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00109-012-0911-2","article-title":"A novel COCH mutation associated with autosomal dominant nonsyndromic hearing loss disrupts the structural stability of the vWFA2 domain","volume":"90","author":"Cho","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/cge.12006","article-title":"Whole exome sequencing identifies a novel DFNA9 mutation, C162Y","volume":"83","author":"Gao","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1002\/humu.22855","article-title":"Novel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion","volume":"36","author":"Jung","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_65","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_66","first-page":"189","article-title":"Novel Mutations in KCNQ4, LHFPL5 and COCH Genes in Iranian Families with Hearing Impairment","volume":"22","author":"Mehregan","year":"2019","journal-title":"Arch. Iran. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41431-020-00724-6","article-title":"Homozygote loss-of-function variants in the human COCH gene underlie hearing loss","volume":"29","author":"Chervinsky","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1007\/s00439-020-02197-5","article-title":"Novel loss-of-function mutations in COCH cause autosomal recessive nonsyndromic hearing loss","volume":"139","author":"Booth","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.amjoto.2012.03.005","article-title":"Etiology of unilateral hearing loss in a national hereditary deafness repository","volume":"33","author":"Dodson","year":"2012","journal-title":"Am. J. Otolaryngol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s00405-019-05322-x","article-title":"A systematic review of hearing and vestibular function in carriers of the Pro51Ser mutation in the COCH gene","volume":"276","author":"Topsakal","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3109\/03005369909090117","article-title":"Non-syndromal autosomal dominant hearing impairment: Ongoing phenotypical characterization of genotypes","volume":"33","author":"Bom","year":"1999","journal-title":"Br. J. Audiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.ajo.2007.01.037","article-title":"Vertical corneal striae in families with authosomal dominant hearing loss: DFNA9\/COCH","volume":"143","author":"Bischoff","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_73","first-page":"66","article-title":"DFNA9\/COCH and its phenotype","volume":"61","author":"Kemperman","year":"2002","journal-title":"Adv. Otorhinolaryngol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.omtn.2021.02.033","article-title":"AON-based degradation of c.151C>T mutant COCH transcripts associated with dominantly inherited hearing impairment DFNA9","volume":"24","author":"Peijnenborg","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2147\/JMDH.S104807","article-title":"Information bias in health research: Definition, pitfalls, and adjustment methods","volume":"9","author":"Althubaiti","year":"2016","journal-title":"J. Multidiscip. Healthc."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1097\/01.mao.0000187240.33712.01","article-title":"Good speech recognition and quality-of-life scores after cochlear implantation in patients with DFNA9","volume":"27","author":"Vermeire","year":"2006","journal-title":"Otol. Neurotol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s00439-003-0992-7","article-title":"Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin","volume":"113","author":"Grabski","year":"2003","journal-title":"Hum. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1136\/jmg.40.7.479","article-title":"Subcellular localisation, secretion, and post-translational processing of normal cochlin, and of mutants causing the sensorineural deafness and vestibular disorder, DFNA9","volume":"40","author":"Robertson","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"14909","DOI":"10.1074\/jbc.M110.106724","article-title":"Role of protein misfolding in DFNA9 hearing loss","volume":"285","author":"Yao","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nmeth.2534","article-title":"The transience of transient overexpression","volume":"10","author":"Gibson","year":"2013","journal-title":"Nat. Methods"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/2\/220\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:08:49Z","timestamp":1760134129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/2\/220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":80,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["biom12020220"],"URL":"https:\/\/doi.org\/10.3390\/biom12020220","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,27]]}}}