Integrative Genetic and Functional Analysis of Autosomal Dominant Hearing Loss in 108 Multigenerational Families

Autosomal dominant hearing loss (ADHL) is a highly heterogeneous Mendelian disorder with numerous causative genes, yet large well-characterized European cohorts remain limited. We investigated 108 families of Polish origin with confirmed dominant inheritance using a tiered strategy integrating targeted sequencing of 237 hearing loss genes, genome-wide linkage analysis, genome sequencing, segregation studies in 437 individuals, and functional validation by minigene splicing assays. This approach established a molecular diagnosis in 52