中文摘要：

目的 对中国人先天性眼外肌纤维化（CFEOM）家系和散发个体进行致病基因突变筛查。 设计 实验研究。研究对象 6个CFEOM家系和4个CFEOM散发个体。 方法 收集CFEOM患者的临床及眼运动神经MRI检查资料，采集患者及家庭成员外周静脉血，提取基因组DNA，应用目标序列捕获联合高通量测序的方法对11个疾病候选基因进行全部外显子的突变筛查。生物信息学分析得到候选基因碱基改变后，在100个无关正常对照人群中进行PCR和Sanger测序验证并对基因型和表型特征进行分析。主要指标 基因序列。 结果 80% （8/10）CFEOM先证者存在KIF21A基因突变，分别为c.2860C〉T（p.R954W）和c.2861G〉A（p.R954Q）；20%（2/10）先证者存在TUBB3基因突变，分别为c.784C〉T （p.R262C）和c.1138C〉T （p.R380C）。所有突变在家系正常个体及正常对照人群中均未检测到。携带KIF21A基因突变的患者表现为CFEOM1A和CFEOM3B表型，而携带TUBB3基因突变的患者表现出CFEOM3A表型。结论 KIF21A基因突变是中国人CFEOM的常见致病原因。高通量基因筛查可快速、准确地协助疾病的临床诊断和基因分型。

英文摘要：

Objective To identify the pathogenic genes of congenital fibrosis of extraocular muscles （CFEOM） in Chinese pedigrees and sporadic patients. Design Experimental study. Participants Six Chinese families and four sporadic patients with CFEOM were enrolled. Methods Clinical data and magnetic resonance imaging （MRI） of the ocular motor nerves were collected. Genomic DNA was isolated from peripheral blood samples of family member. Mutation analyses of eleven candidate genes were performed to detect the potential mutation by using targeted exome sequencing. After bioinformatic analysis, the nucleotide substitutions of candidate genes were verified by polymerase chain reaction （PCR） and Sanger sequencing in 100 unrelated normal control individuals, then the analysis for genotype-phenotype correlation was performed. Main Outcome Measures Gene sequences. Results We identified two heterozygous KIF21A mutations c.2860C〉T（p.R954W） and c.2861G〉A（p.R954Q） in 80% （8/10） probands;two heterozygous TUBB3 mutations c.784C〉T （p.R262C） and c.1138C〉T （p.R380C） in 20%（2/10） probands. These changes were not found in normal family members and 100 normal control individuals. The patients with KIF21A mutations showed phenotypes of CFEOM1A and CFEOM3B, however the patients with TUBB3 mutations showed CFEOM3A. Conclusions KIF21A gene mutations are the leading cause of Chinese CFEOM patients. High throughput gene screening could assist clinical diagnosis and phenotyping quickly and accurately.