Genetic Findings in Seven Cochlear Implanted Patients with Severe-to-Profound Hearing Loss

Background/Objectives: Hearing loss is one of the most prevalent sensory disorders in humans, with genetic factors accounting for approximately 60% of cases. Cochlear implantation is an effective intervention for individuals with severe-to-profound hearing loss. However, substantial variability in postoperative auditory performance persists, complicating the prediction of individual outcomes. This study investigated the genetic findings associated with hearing loss in a cohort of seven affected adults with cochlear implants (CIs). Methods: A total of seven patients with severe-to-profound hearing loss underwent genetic testing. Two of them were part of diagnostic screening, and five of them were part of research genetic analyses. Results: High-throughput genomic DNA sequencing identified twelve variants across multiple genes, including four new sequence variants. Based on ACMG/AMP criteria, integrating computational predictions, population frequency data, ClinVar annotations, and in silico pathogenicity assessments, the identified variants were classified as pathogenic variants, likely pathogenic variants, and variants of uncertain significance (VUS). We detected one pathogenic variant, two likely pathogenic variants and nine variants of uncertain significance (VUS). Novel variants were further analyzed using multiple sequence alignment to assess evolutionary conservation. Conclusions: The identification of four novel variants within the analyzed patients underscores the genetic heterogeneity of hearing loss and the importance of genetic analyses for improving the understanding of its molecular basis. Further functional and clinical studies are required to determine the pathogenicity of these variants and their potential clinical relevance.