遗传性耳聋（HHL）相关致病单基因已发现100余个，其分布具有地域和种族差异性。云南多民族耳聋人群缺乏系统的遗传学研究，我们发现最为常见的HHL致病基因GJB2在云南汉族和多个少数民族耳聋群体中的致病率有差异，同时其在各民族间的致病率也有异同，提示云南耳聋人群的HHL致病基因分布有待探究。在本项目中，我们将收集云南汉族和主要少数民族（哈尼，白，傣、彝）疑似HHL患者的外周血样本600份，借助二代测序技术对上述GJB2突变热点阴性的耳聋患者进行HHL相关127个致病基因的测序和生物信息学分析，依据ACMG标准判定检出的基因突变和变异，统计和分析多民族间致聋基因的分布、致病率及其突变/变异类型特点，同时对发现的高风险致聋新变异（如民族中占主导的新致聋变异）进行家系分析和功能验证（CRISPR/Cas9技术）。本研究将进一步解析云南多民族耳聋人群中的HHL致病基因分布，为云南耳聋预防提供依据。

More than one hundred single pathogenic genes have been identified in hereditary hearing loss (HHL). The distribution of these pathogenic genes has been shown to be different in populations of various regions and races. The molecular genetics in multiple ethnic deaf populations of Yunnan Province is rarely studied. We found that GJB2, the most common pathogenic gene of HHL, shows different pathogenic rates between Han and multiple minorities’ deafness populations in Yunnan province. Meanwhile, the pathogenic rates of GJB2 gene show differences and similarities among multiple ethnic deaf populations of Yunnan province. It suggested that the distribution of HHL pathogenic genes in deaf populations needs to be further studied in Yunnan provinces. In this study, we will collect 600 peripheral blood samples of suspected deaf patients including Han, Hani, Bai, Dai and Yi nations in Yunnan province. Based on the next generation sequencing technology, the 127 pathogenic genes of HHL will be sequenced and bioinformatically analyzed on the above deaf patients without GJB2 hot mutations related to HHL. The mutations and variations will be examined according to the ACMG Guidelines. After statistical analysis, the distribution discrepancy and pathogenic rates of HHL pathogenic genes and its mutations/variations characteristics will be revealed in the multiple ethnic populations of Yunnan province. The novel and high-risk variations of HHL (the novel predominat deaf variations in nations, etc) will be further confirmed by using pedigree analysis and functional verification with CRISPR/Cas9-mediated genome editing technique. This study will further reveal the distribution and characteristics of HHL pathogenic genes in Yunnan deaf populations. It will provide the evidences for the prevention of deafness in Yunnan province.