COCH, also known as coagulation factor C homolog, encodes for cochlin, a protein abundantly expressed in the spiral ligament and spiral limbus of the inner ear [3]. Its function is not fully understood, but it is associated with the development of progressive sensorineural hearing loss and vestibular dysfunction [3]. Pathogenic missense variants in COCH are linked to DFNA9, an autosomal dominant inherited disorder [1].

Functional studies demonstrated distinct pathogenic mechanisms for COCH variants in a domain-dependent manner. For example, the p.Phe230Leu variant, located in the vWFA1 domain, showed a cytotoxic effect [2]. Different mouse models were developed to understand the pathology of DFNA9 better. It is believed that COCH mutations affect the intracellular trafficking of cochlin, which could explain the characteristic acellular eosinophilic deposits seen in the temporal bones of DFNA9 patients [3].

In conclusion, COCH plays a crucial role in inner ear function, and its variants are associated with DFNA9-related sensorineural hearing loss and vestibular dysfunction. The use of mouse models has been valuable in uncovering the pathogenic mechanisms associated with COCH variants, providing insights into the underlying pathology of DFNA9 [3].