中国人先天性眼球震颤家系的致病基因分析

Congenital nystagmus(CN) is primarily a disorder defined as conjugated, spontaneous, and involuntary ocular oscillations, causing great damage to patients' visual development. The pathogenic mechanism needs futher research. Phathogenic genes remain unknown in more than one half of the patients. Study on the pathogenic genes will help explore the pathogenesis, and provide basis for prenatal diagnosis and early treatment. We've collected several Chinese CN families and a large number of sporadic cases, and screened the known pathogenic genes and loci in some of the families. In this study, we will focus on seeking new gene/genes associated with this disease through linkage analysis, candidate cloning and target capture sequencing. Futher we'll explore the functions of the coding protein and investigate its pathogenic mechanism.

先天性眼球震颤（Congenital Nystagmus，CN）是一种不自主的有节律的眼球的摆动，严重损害了婴幼儿的视觉发育。其发病机制有待研究，目前至少有超过一半的患者其致病基因难以明确。对其致病基因的研究是探索发病机制的基础，将为寻求产前诊断和早期治疗提供依据。我们已收集了多个中国人先天性眼球震颤的大家系及大量的散发病例，并对部分家系进行了已知致病基因和位点的筛查，本研究拟通过遗传性标志物连锁分析，结合候选基因克隆和靶向捕获高通量测序的方法鉴定家系的致病基因，并对其编码蛋白的功能进行研究，阐明致病机理。

背景：先天性眼球震颤是由于眼球运动传出或传出机制障碍所致的眼球不自主、有节律的运动，常于出生后或婴幼儿期发病。根据发病机制不同主要分为先天性特发性眼球震颤和知觉缺陷性眼球震颤。研究内容：分析先天性眼球震颤家系的致病基因突变。收集了16个先天性眼球震颤家系，抽取静脉血、提取基因组DNA，通过Sanger测序法和全外显子组测序的方法检测先天性眼球震颤家系的致病突变，并进行初步功能分析。重要结果及数据：我们在其中四个家系中筛选出6个致病突变：家系1 FRMD7基因c.902 A>G；家系2 FRMD7基因c.1944T>A、1945G>T；家系3 NYX基因c.887_c.888delGC；家系4 USH2A基因：c.2310_2311insA和c.8559-2A>G，其中有4个既往文献中未见报道的新突变，本项目研究进一步扩展了先天性特发性眼球震颤致病基因的突变谱，同时对家系进行遗传咨询，具有一定的临床意义。