목적: Postlingual progressive hearing loss mostly shows autosomal dominant inheritance. Up to date, there are about 30 genes which cause autosomal dominant nonsyndromic hearing loss (AD-NSHL). DFNA9 is autosomal dominant disorder characterized by a late onset, non-syndromic hearing loss and vestibular dysfunction. Mutations in the COCH gene encoding cochlin are etiologically linked to DFNA9. However, the physiological role of cochlin in inner ear is still unknown. Here, we identify the pathologic mechanism of DFNA9-associated mutations and suggest the possible physiological role of cochlin in inner ear. 방법:We designed genetic screening flow chart for Korean AD-NSHL patients, specifically focused on the cost effective and simplified strategy for small sized family studies as to whole exome sequencing. For the functional study, we transfected mutant cochlins including novel variant in HEK293 cells and analyzed the cellular expression and the matrix metalloproteinase cleavage activity. 결과:As we followed the genetic screening protocol, we found an AD-NSHL family. We performed whole exome sequencing of only two affected patients, identified 26 novel variants among the known genes of AD-NSHL. After filtering out single nucleotide polymorphism (SNP) with dbSNP or 1000 genomes, we were able to leave only two variants, p.V123E in COCH and p.A77T in TPRN. After Sanger validation of the variants in two affected patients and 4 unaffected controls, we designated p.V123E of COCH as the causing gene of progressive hearing loss in this family. Followed functional data of p.V123E COCH strongly supports that p.V123E could progressively deteriorate hearing function. 결론:Novel variant p.V123E of COCH is resistant to the cleavage by matrix metalloproteinase and causes DFNA9.