{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:05:31Z","timestamp":1779379531858,"version":"3.53.1"},"reference-count":17,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objectives: To characterize heterozygous pathogenic COCH variants in a French cohort with non-syndromic sensorineural hearing loss (NSHL) and assess genotype\u2013phenotype correlations in autosomal dominant NSHL (DFNA9). Setting: National Reference Center for Genetic Hearing Loss, Necker\u2013Enfants Malades Hospital, Paris, France. Methods: This retrospective observational study included 69 individuals from 20 unrelated families diagnosed with DFNA9 (2005\u20132025). All individuals underwent clinical and audiological evaluations and genetic testing via targeted COCH Sanger sequencing or next-generation sequencing (NGS) panels. Variants were interpreted according to ACMG guidelines. Audiometric profiles and vestibular data were collected. Results: Seven known pathogenic COCH variants were found in ten families, and ten novel likely pathogenic variants in the others. Variants in vWFA domains were associated with early or late onset, progressive, bilateral and symmetrical hearing loss. Three variants (p.Gln410Arg, p.Ile450Val, p.Cys542Arg) were associated with congenital or prelingual onset, an atypical DFNA9 presentation. Variants in the LCCL domain were associated with later-onset hearing loss and more frequent vestibular dysfunction. Vestibular abnormalities were observed in about half of early-onset cases. Conclusions:COCH-related hearing loss is a rare cause of autosomal dominant NSHL, with only 20 families identified over two decades within the French network. This study expands the mutational spectrum of COCH by reporting ten novel variants and supports a domain-specific genotype\u2013phenotype correlation. These findings improve the understanding of DFNA9 variability and have direct implications for clinical diagnosis, prognosis, and genetic counseling.<\/jats:p>","DOI":"10.3390\/genes17050588","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:02:27Z","timestamp":1779375747000},"page":"588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["COCH-Related Hearing Loss in a French Cohort: Novel Variants and Genotype\u2013Phenotype Correlations"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1704-577X","authenticated-orcid":false,"given":"Ralyath","family":"Balogoun","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine for Rare Diseases, Necker\u2013Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"},{"name":"National Reference Center for Genetic Hearing Loss, Necker\u2013Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-0872","authenticated-orcid":false,"given":"Margaux","family":"Serey-Gaut","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine for Rare Diseases, Necker\u2013Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"},{"name":"National Reference Center for Genetic Hearing Loss, Necker\u2013Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7064-0765","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Pingault","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine for Rare Diseases, Necker\u2013Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Lemiere","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine for Rare Diseases, Necker\u2013Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Lina-Granade","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Audiophonology, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffroy","family":"Delplancq","sequence":"additional","affiliation":[{"name":"Constitutional Genetics Unit, Versailles Hospital, 78150 Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Guerrot","sequence":"additional","affiliation":[{"name":"Inserm U1245, Department of Genetics and Reference Center for Developmental Disorders, Normandie University, University of Rouen Normandy, Rouen University Hospital (CHU Rouen), 76031 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-5300","authenticated-orcid":false,"given":"Annick","family":"Toutain","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Tours University Hospital (CHRU Tours), 37044 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Dupin-Deguine","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Otoneurology and Pediatric Otorhinolaryngology, University of Toulouse, Purpan University Hospital (CHU Purpan), 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Legendre","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Bordeaux University Hospital (CHU de Bordeaux), 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Colin","sequence":"additional","affiliation":[{"name":"Inserm, CTM UMR1231, GAD Team, FHU TRANSLAD, Department of Genetics, Reference Center for Developmental Anomalies and Congenital Malformation Syndromes, Universit\u00e9 Bourgogne, Dijon University Hospital (CHU Dijon Bourgogne), 21079 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Loundon","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otorhinolaryngology and Head and Neck Surgery, Necker\u2013Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Paris Cit\u00e9 University, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0369-0505","authenticated-orcid":false,"given":"Laurence","family":"Jonard","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine for Rare Diseases, Necker\u2013Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"},{"name":"National Reference Center for Genetic Hearing Loss, Necker\u2013Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-9806","authenticated-orcid":false,"given":"Sandrine","family":"Marlin","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine for Rare Diseases, Necker\u2013Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"},{"name":"National Reference Center for Genetic Hearing Loss, Necker\u2013Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France"},{"name":"Genetics of Rare Ophthalmological, Auditory and Mitochondrial Disorders, Inserm UMR_S1163, Imagine Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","unstructured":"(2025, December 15). 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