由COCH基因突变导致的迟发性遗传性聋颞骨病理显示内耳退行性变，而突变基因蛋白的错折叠是导致某些神经退行性疾病的重要原因，推测COCH基因突变蛋白的错折叠及代谢异常可能是内耳功能障碍的发病机制。本研究在已发现COCH基因突变的基础上，拟采用构建突变位于不同结构域的COCH基因表达质粒转染细胞系，以及构建与人致病突变相对应的鼠突变COCH基因病毒表达载体转染鼠内耳，通过蛋白印迹、ELISA、质谱分析等方法检测细胞培养液、细胞裂解液以及鼠内耳组织突变Cochlin蛋白各同工型的含量，同时监测耳蜗功能，探讨COCH基因不同突变蛋白是否影响其在细胞外基质中的整合。进一步以胶原蛋白为靶位，采用等离子共振、光谱分析和免疫共沉淀等方法鉴定Cochlin蛋白的互作蛋白，探讨Cochlin蛋白在内耳的作用，从而阐明COCH基因突变致迟发性聋的发病机制，为进一步探讨迟发进展性遗传性聋的药物治疗提供依据。

Pathological studies of the temporal bones from individuals affected by COCH gene mutation have shown remarkable degeneration of neuroepithelial cells. Protein misfolding is a fundamental mechanism underlying multiple chronic neurodegenerative diseases. Therefore, one of the pathogenesis of late-set progressive hereditary hearing loss might be a misfolding and metabolic disorder of mutant cochlin. On the basis of finding the novel mutation of COCH gene, the wild and mutant COCH gene will be constructed and transfected to cultivating cells and cochlea in vivo with AAV vector, and quality and quantity of wild and mutant cochlin will be detected with Western bolting, ELISA, mass spectrometry analysis, and monitoring the cochlear function in the present study, to explore integration of mutant cochlin into the extracellular matrix. Further, interact protein of cochlin protein will be appraised with collagen protein, by using surface plasmon resonance analysis, dichroism spectroscopy analysis and immunoprecipitation, to explore the role of cochlin protein in the inner ear. Thus it will be clarified that the pathogenesis of COCH gene mutations is responsible for late-set progressive hearing loss.