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The clinical presentation of these conditions spans a spectrum, ranging from mild to profound hearing loss. The aim of this study was to identify the genetic cause of hearing loss in a family and functionally validate a novel variant identified in the MYO6 gene. After Whole Exome Sequencing analysis, the variant c.2775G&amp;gt;C p.Arg925Ser in MYO6 was detected in a family with postlingual non-syndromic hearing loss. By protein modeling a change in the electrostatic charge of the single alpha helix domain surface was revealed. Through a knockdown phenotype rescue assay in zebrafish, the detrimental effects of the identified variant on the auditory system was determined. These findings underscore the significance of a comprehensive approach, integrating both in silico and in vivo strategies, to ascertain the pathogenicity of this candidate variant. Such an approach has demonstrated its effectiveness in achieving an accurate genetic diagnosis and in promoting a more profound comprehension of the mechanisms that underlie the pathophysiology of hearing.<\/jats:p>","DOI":"10.1093\/nargab\/lqae162","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T18:12:00Z","timestamp":1733940720000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>In silico<\/i> and <i>in vivo<\/i> analyses of a novel variant in <i>MYO<\/i>6 identified in a family with postlingual non-syndromic hearing loss from Argentina"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2985-4790","authenticated-orcid":false,"given":"Paula\u00a0I","family":"Buonfiglio","sequence":"first","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda y Gen\u00e9tica de la Audici\u00f3n, Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular \u201cDr. H\u00e9ctor N. Torres\u201d (INGEBI), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) , Ciudad Aut\u00f3noma de Buenos Aires, C1428ADN,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-5418","authenticated-orcid":false,"given":"Carlos\u00a0D","family":"Bruque","sequence":"additional","affiliation":[{"name":"Unidad de Conocimiento Traslacional Hospitalaria Patag\u00f3nica, Hospital de Alta Complejidad SAMIC , El Calafate, Provincia de Santa Cruz, 9405 ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-9856","authenticated-orcid":false,"given":"Luc\u00eda","family":"Salatino","sequence":"additional","affiliation":[{"name":"Instituto de Farmacolog\u00eda, Facultad de Medicina, Universidad de Buenos Aires , Ciudad Aut\u00f3noma de Buenos Aires, C1121ABG ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-5426","authenticated-orcid":false,"given":"Vanesa","family":"Lotersztein","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital Militar Central \u201cDr. Cosme Argerich\u201d , Ciudad Aut\u00f3noma de Buenos Aires, C1426 ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4674-1275","authenticated-orcid":false,"given":"Mariela","family":"Pace","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda y Gen\u00e9tica de la Audici\u00f3n, Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular \u201cDr. H\u00e9ctor N. Torres\u201d (INGEBI), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) , Ciudad Aut\u00f3noma de Buenos Aires, C1428ADN,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8265-9003","authenticated-orcid":false,"given":"Sofia","family":"Grinberg","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda y Gen\u00e9tica de la Audici\u00f3n, Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular \u201cDr. H\u00e9ctor N. Torres\u201d (INGEBI), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) , Ciudad Aut\u00f3noma de Buenos Aires, C1428ADN,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-0311","authenticated-orcid":false,"given":"Ana\u00a0B","family":"Elgoyhen","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda y Gen\u00e9tica de la Audici\u00f3n, Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular \u201cDr. H\u00e9ctor N. Torres\u201d (INGEBI), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) , Ciudad Aut\u00f3noma de Buenos Aires, C1428ADN,","place":["Argentina"]},{"name":"Instituto de Farmacolog\u00eda, Facultad de Medicina, Universidad de Buenos Aires , Ciudad Aut\u00f3noma de Buenos Aires, C1121ABG ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8195-484X","authenticated-orcid":false,"given":"Paola\u00a0V","family":"Plazas","sequence":"additional","affiliation":[{"name":"Instituto de Farmacolog\u00eda, Facultad de Medicina, Universidad de Buenos Aires , Ciudad Aut\u00f3noma de Buenos Aires, C1121ABG ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5283-4726","authenticated-orcid":false,"given":"Viviana","family":"Dalam\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda y Gen\u00e9tica de la Audici\u00f3n, Instituto de Investigaciones en Ingenier\u00eda Gen\u00e9tica y Biolog\u00eda Molecular \u201cDr. H\u00e9ctor N. 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