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Its prevalence varies by region and ethnicity, with scarce epidemiological data in the Brazilian population. Although most MD cases are sporadic, familial MD (FMD) is observed in 5% to 20% of European cases. Through exome sequencing, we have found a rare missense variant in the OTOG gene in a Brazilian individual with MD with probable European ancestry (chr11:17599671C&gt;T), which was previously reported in a Spanish cohort. Two additional rare missense heterozygous OTOG variants were found in the same proband. Splice Site analysis showed that chr11:17599671C&gt;T may lead to substantial changes generating exonic cis regulatory elements, and protein modelling revealed structural changes in the presence of chr11:17599671C&gt;T, chr11:17576581G&gt;C, and chr11:17594108C&gt;T, predicted to highly destabilize the protein structure. The manuscript aims to replicate genes previously reported in a Spanish cohort, and the main finding is that a Brazilian patient with MD also has variants previously reported in familial MD, supporting OTOG as the most frequently mutated gene in MD.<\/jats:p>","DOI":"10.3390\/genes16060654","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T03:30:19Z","timestamp":1748489419000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Replication of Missense OTOG Gene Variants in a Brazilian Patient with Meni\u00e8re\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1762-6988","authenticated-orcid":false,"given":"Giselle","family":"Bianco-Bortoletto","sequence":"first","affiliation":[{"name":"Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2064, Australia"},{"name":"Laboratory of Human Molecular Genetics, Center for Molecular Biology and Genetic Engineering\u2014CBMEG, State University of Campinas\u2014UNICAMP, Campinas 13083-875, SP, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias M\u00e9dicas, Faculty of Medical Sciences, State University of Campinas\u2014UNICAMP, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2715-3670","authenticated-orcid":false,"given":"Geovana","family":"Almeida-Carneiro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Tissue Biology, Laboratory of Paracrine Signalling in Tissue Organisation\u2014SPOT, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biologia Molecular e Morfofuncional, Biology Institute, State University of Campinas\u2014UNICAMP, Campinas 13083-862, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Fabbri-Scallet","sequence":"additional","affiliation":[{"name":"Laboratory of Human Molecular Genetics, Center for Molecular Biology and Genetic Engineering\u2014CBMEG, State University of Campinas\u2014UNICAMP, Campinas 13083-875, SP, Brazil"},{"name":"Postdoctoral Researcher Program, Faculty of Medical Sciences, State University of Campinas\u2014UNICAMP, Campinas 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1208-8348","authenticated-orcid":false,"given":"Alberto M.","family":"Parra-Perez","sequence":"additional","affiliation":[{"name":"Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2064, Australia"},{"name":"Otology & Neurotology Group CTS495, Division of Otolaryngology, Department of Surgery, Instituto de Investigaci\u00f3n Biosanitaria, ibs.GRANADA, Granada, Universidad de Granada, 18012 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen de Carvalho","family":"Lopes","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04038-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana de Almeida Lima S\u00e1","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04038-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-9818","authenticated-orcid":false,"given":"Fernando Freitas","family":"Ganan\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04038-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-8607","authenticated-orcid":false,"given":"Juan Carlos","family":"Amor-Dorado","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Hospital Can Misses, 07800 Ibiza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-329X","authenticated-orcid":false,"given":"Andres","family":"Soto-Varela","sequence":"additional","affiliation":[{"name":"Division of Neurotology, Department of Otorhinolaryngology, Complexo Hospitalario Universitario, 15706 Santiago de Compostela, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialities, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1430","authenticated-orcid":false,"given":"Jose A.","family":"Lopez-Escamez","sequence":"additional","affiliation":[{"name":"Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2064, Australia"},{"name":"Otology & Neurotology Group CTS495, Division of Otolaryngology, Department of Surgery, Instituto de Investigaci\u00f3n Biosanitaria, ibs.GRANADA, Granada, Universidad de Granada, 18012 Granada, Spain"},{"name":"Sensorineural Pathology Programme, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edi 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