International Session 3 Head and Nack-Basic 1

Sensorineural hearing loss(SNHL)is a prevalent sensory disorder with a high Mendelian genetic contribution.Despite advances in our understanding of genetic factors affecting SNHL, the genomic landscape and associated phenotypic attributes of SNHL remained unresolved.Here we explored the genetic foundation of 394 SNHL families, using a stepwise approach from targeted sequencing to whole-genome sequencing(WGS) .Collectively, complete genetic diagnosis was made over 70 ％.Among patients undiagnosed by targeted sequencing, WGS revealed causal variants in additional 23． 6％ which were otherwise challenging to detect, and also identified previously unrecognized genetic variants in novel genes.Intriguingly, complete genetic diagnosis achieved through WGS provided additional clinical options for all of the patients, including targeted agents(e.g., gene editing) , referral to specialists, tailored auditory rehabilitation, reproductive consultation, or symptomatic treatment.WGS was most useful in patients demonstrating specific clinical and genetic features-including early age-of-onset, presence of syndromic features, and detection of suggestive, but insufficient genetic diagnosis from targeted approaches.