Domestic researchers have identified the genetic causes of sensorineural hearing loss and newly constructed a genetic map of hearing loss for Koreans. The results of this study are significant as they may contribute to the development of gene-based personalized treatment methods in the future.
Sensorineural hearing loss is hearing loss caused by problems in the nerve transmission between the auditory nerve and the brain. The genetic causes of hearing loss are very diverse and complex, making it difficult to identify genetic causes in about 50% of patients with existing testing methods. To develop accurate diagnoses and personalized treatment methods, a wider range of genetic variant analysis is necessary.
Seoul National University Hospital announced on the 3rd that Professor Lee Sang-yeon from the Department of Otorhinolaryngology and Professors Chae Jong-hee and Lee Seung-bok from the Department of Clinical Genomics have identified the genetic causes of sensorineural hearing loss through precise genetic analysis of 394 households (752 individuals) of hearing loss patients at the hospital. The research results were published in the latest issue of Cell Report Medicine.
The research team confirmed key genes like GJB2 through a stepwise genetic testing approach using single-gene PCR tests. They then analyzed a broader range of genes through target panel testing (TPS) and whole exome sequencing (WES), and in the final stage, identified structural variants and deep intronic variants (non-coding region variants) that were not detected by existing tests (TPS, WES) through whole genome sequencing (WGS).
Using this method, they identified the genetic causes in 219 households out of the 394 households with sensorineural hearing loss. In particular, they discovered additional variants in 19.2% (44 households) that had not been identified by existing precision testing methods, thus improving the diagnostic rate of hereditary hearing loss by about 20%. The whole genome analysis uncovered variants missed by existing tests, increasing the overall diagnostic rate.
This study also confirmed, for the first time, non-coding region variants such as deep intronic variants and structural variants. Deep intronic variants are changes that occur in non-coding regions beyond the boundaries of exons and introns, which are crucial for protein production. These were areas that could not be examined by existing testing methods.
This discovery is being evaluated as providing new insights into the genetic causes of hearing loss. In particular, three new deep intronic variants found in the USH2A gene, a representative gene for Usher syndrome, caused splicing errors that impacted protein production. This could lead to the development of RNA gene therapies targeting deep intronic variants.
Professor Lee Sang-yeon of the Department of Otorhinolaryngology at Seoul National University Hospital said, "Through this research, we were able to confirm the causes of many undiagnosed hearing loss patients, and we have discovered a cohort of patients who can receive gene therapy," adding, "We will actively utilize whole genome analysis to continue to address the undiagnosed causes of hearing loss, leading to precise treatment for childhood hearing loss."
Meanwhile, this research was conducted with support from the 'Lee Kun-hee Childhood Cancer and Rare Disease Research Project' and the 'National Research Foundation of Korea (NRF) Excellent Early-Career Research' initiative.
Reference material
Cell Report Medicine (2025), DOI: https://doi.org/10.1016/j.xcrm.2025.102206