重度-极重度感音神经性耳聋是导致言语交流障碍的常见致残性疾病，是全球关注的重大公共卫生问题。"诊聋、防聋、治聋"不仅关系到千家万户的幸福，也关系到社会经济的健康发展。本课题拟在完善全国性大规模耳聋分子流行病学调查研究的基础上，对中国人群耳聋，特别是重度-极重度感音神经性耳聋的分子致病机制进行较为全面的研究，利用外显子捕捉、生物编码和大规模平行测序技术在中国聋人群体针对215个已知耳聋基因和耳聋相关基因进行遗传分析及突变谱绘制。对经上述分析仍不能明确分子病因的患者群，利用全外显子组测序结合生物信息学分析方法在全基因组编码区寻找重要的常染色体隐性遗传耳聋新基因，并研究其功能和致病机制，绘制较为详细的中国人群重度-极重度感音神经性耳聋的基因谱，针对中国人群重要致聋基因，探索基因治疗新方法。研究结果将用于指导耳聋的临床诊断和干预，为实现耳聋的防治、减少耳聋出生缺陷提供理论基础和技术支持。

Sensorineural hearing loss affects the ability of communication and quality of life of millions of people. Prevention of its occurrence is the key to solving this problem. However, the majority of hearing defect cases are considered idiopathic and their genetic basis remian unknow. Based upon the accomplishment of nationwide molecular epidemiological investigation of hearing loss, we are going to make further research on comprehensive molecular pathogenesis for Chinese deaf population.The techniques of exone capture, barcode and massively parallel sequencing will be used to study up to 200 known deaf genes in our cohorts. Whole- exome sequencing will be used to explore the possible new deaf genes in cases without clear disease causing mutations found in previous steps and the function and pathogenic pathway of these new deaf genes will be studied. Strategy of gene therapy of the common hereditary hearing impairments will be also studied. The outcome of this study will provide fundamental basis of clinical diagnosis and intervention of deafness.