Usher综合征 (Usher syndrome, USH) 是最常见的一种综合征性视网膜色素变性, 其在盲聋患者中比例高达50%。随着分子遗传学的发展，基因治疗将成为其潜在的治疗方法，因此快速准确基因诊断对USH患者十分重要。USH具有高度临床和遗传异质性，加之其USH致病基因多样及致病突变形式复杂，传统基因突变分析方法很难对USH患者进行快速准确分子遗传学诊断。本研究将在前期工作基础上用高通量二代测序技术的目标区域外显子组测序或全外显子组测序,结合Sanger-DNA测序，探针连接多重扩增等实验技术对大样本量USH患者进行全面深入致病基因突变分析，旨在确定国人各型USH患者致病基因突变特点和基因突变谱，发现新的致病基因，建立基因型与表型间关系，为USH患者提供准确分子遗传诊断，为患者将来进行基因治疗奠定基础，为患者家系成员提供相应的临床咨询。

Usher syndrome (USH) is the most common syndromic- retinitis pigmentosa, representing approximately 50% of adult cases with deaf- blindness. With the genetic research progressing, gene therapy will be a potential method for patients with USH, therefore, it is very important for the patients having a rapid and accurate molecular diagnosis. USH is extremely clinical and genetic heterogeneous, it is very difficult to get a rapid and accurate molecular diagnosis for USH patients using conventional mutation analysis methods. The current study will do comprehensive mutation analysis in a large cohort of patients with USH by targeted exome sequencing or whole exome sequencing combined with some routine analysis methods such as Sanger DNA sequencing and multiplex ligation-dependent probe amplification. The purpose of this study is to determine the mutation spectrum, identify the new USH-causing disease gene, and define the correlations between the genotype and phenotype. The results will provide the accurate molecular diagnosis for patients with USH, which are foundations for their future gene therapy, and provide genetic consultant for their family members.