and Analyses of a Novel Variant in 6 Identified in a Family with Postlingual Non-syndromic Hearing Loss from Argentina

Hereditary hearing loss stands as the most prevalent sensory disorder, with over 124 non-syndromic genes and approximately 400 syndromic forms of deafness identified in humans. 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 6 gene. After Whole Exome Sequencing analysis, the variant c.2775G>C p.Arg925Ser in 6 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 and 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.