先天性白内障伴听力损害综合征致病基因的研究

Congenital cataract is one of the major cause of blindness and syndromic hearing impairment is one of the main factors affecting human hearing.So far, many patients are suffering from congenital cataract with hearing impairment syndrome, and there is no effective prevention and treatment for this disease. Also, there is no convincing responsible genes identified yet. Therefore, it is very important to reveal its etiology and pathological mechanism. We have collected several pedigrees with congenital cataract with hearing impairment syndrome, one of which have been analyzed by cytogenetic and chip CNV method. The preliminary results showed that the congenital cataract with hearing impairment syndrome in this family was caused by Y chromosome genetic mode. This study is to identify the disease gene and to investigate the pathogenesis of congenital cataract with hearing impairment syndrome caused by Y-chromosome mutation, which could provide new approaches and targets for disease prevention, prenatal diagnosis and treatment, and also have an important role in clinical drug development.

先天性白内障是主要致盲眼病之一；综合征型听力损害是影响听力的主要原因之一。先天性白内障伴听力损害综合征严重影响患者生存质量，迄今为止尚无有效的预防和治疗手段。对其病因、病理机制的研究是解决先天性白内障伴听力损害综合征问题的关键。尚无明确公认的先天性白内障伴听力损害综合征的致病基因。我们在已经收集了几个先天性白内障伴听力损害综合征家系病人资料的基础上，对其中的一个大家系进行了细胞遗传学和芯片CNV分析，根据家系的遗传规律和前期结果，发现该家系为Y染色体遗传所引起的先天性白内障伴听力损害综合征。本研究拟用专门的Y染色体分析方法，鉴定其疾病基因并进行发病机制研究，为先天性白内障伴听力损害综合征预防、产前诊断和治疗奠定基础，同时疾病基因产物可作为有价值的靶标以开发新药。

先天性白内障伴听力损害综合征严重影响患者生存质量，对其发病机制的研究是解决先天性白内障伴听力损害综合征问题的关键。本课题在采集先天性白内障伴听力损害综合征患者家系和散发病例资料及样本的基础上，通过建立先天性白内障伴听力损害综合征患者、对照者信息体系，结合全基因组外显子测序、10X重测序、染色体结构分析、流式细胞仪分选、全基因组扫描及连锁分析等先进技术，运用sanger测序等对其进行验证，对家系的已知先天性白内障伴听力损害综合征位点及新位点进行了筛查，对常染色体区域和性染色体 (主要是Y染色体)区域疾病基因位点的候选基因及其突变进行了较深入分析，对发病机制的研究，为先天性白内障伴听力损害综合征预防、产前诊断和治疗奠定基础。