목적: Congenital hearing loss is predominantly driven by monogenic causes with a high Mendelian contribution. Nevertheless, digenic inheritance has been increasingly recognized as a substantial contributor to the genetic etiology of hearing loss, although its precise prevalence and functional epistasis remain poorly understood. In this study, we investigate the clinical phenotypes and genotypes of digenic mutations associated with sensorineural hearing loss (SNHL) in a large cohort and evaluate the molecular interactions among implicated gene pairs. 방법:We examined data from 821 SNHL families who underwent whole-exome or whole-genome sequencing, focusing on potential second hits in cases previously diagnosed with monogenic deafness. Bioinformatic analyses and structural modeling of the implicated gene pairs (i.e., modifying digenic and double diagnosis) were performed to elucidate the molecular interactions and pathogenic mechanisms involved. Additionally, we assessed how digenic inheritance influences phenotypic outcomes. 결과:A substantial proportion of digenic inheritance was identified, and novel digenic gene pairs were discovered. In modifying digenic cases, the combined mutations were associated with more severe phenotypes compared to monogenic mutations. Moreover, digenic mutations in the double-diagnosis cases expanded the previously uncharacterized phenotypic spectrum. Functional analyses of these gene pairs revealed potential molecular interactions that underlie the observed phenotypic variation. 결론:This study provides new insights into the profiles of digenic inheritance in SNHL. By identifying new digenic pairs and exploring their molecular interaction mechanisms, we further elucidate how digenic inheritance modifies clinical phenotypes and its broader clinical implications.