PDF(Pubmed)
Abstract：
The USH2A gene encodes usherin, a basement membrane protein that is involved in the development and homeostasis of the inner ear and retina. Mutations in USH2A are linked to Usher syndrome type II (USH II) and non-syndromic retinitis pigmentosa (RP). Molecular diagnosis can provide insight into the pathogenesis of these diseases, facilitate clinical diagnosis, and identify individuals who can most benefit from gene or cell replacement therapy. Here, we report 21 pathogenic mutations in the USH2A gene identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology.
In all, 11 unrelated Chinese families were enrolled, and NGS was performed to identify mutations in the USH2A gene. Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations in these families.
We identified 21 pathogenic mutations, of which 13, including 5 associated with non-syndromic RP and 8 with USH II, have not been previously reported. The novel variants segregated with disease phenotype in the affected families and were absent from the control subjects. In general, visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations.
These findings provide a basis for investigating genotype-phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.
In all, 11 unrelated Chinese families were enrolled, and NGS was performed to identify mutations in the USH2A gene. Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations in these families.
We identified 21 pathogenic mutations, of which 13, including 5 associated with non-syndromic RP and 8 with USH II, have not been previously reported. The novel variants segregated with disease phenotype in the affected families and were absent from the control subjects. In general, visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations.
These findings provide a basis for investigating genotype-phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.
摘要：
USH2A基因编码usherin，一种基底膜蛋白，参与内耳和视网膜的发育和稳态。USH2A中的突变与Usher综合征II型（USHII）和非综合征性色素性视网膜炎（RP）有关。分子诊断可以提供对这些疾病的发病机制的见解，促进临床诊断，并确定能从基因或细胞替代疗法中获益最多的个体。这里,我们报告了使用靶向下一代测序(NGS)技术在11个中国家庭中鉴定的USH2A基因中的21个致病突变.
总之,11个不相关的中国家庭被登记，并进行NGS以鉴定USH2A基因中的突变。变异分析,Sanger验证,和隔离测试被用来验证这些家族的致病突变。
我们确定了21个致病突变，其中13例，包括5例与非综合征性RP相关，8例与USHII相关，以前没有报道过。在受影响的家庭中，新的变体与疾病表型分离，并且在对照受试者中不存在。总的来说,视觉障碍和视网膜病变在USHII和有USH2A突变的非综合征型RP患者之间是一致的.
这些发现为研究中国USHII和RP患者的基因型-表型关系以及阐明与USH2A突变相关的疾病的病理生理学和分子机制提供了基础。
总之,11个不相关的中国家庭被登记，并进行NGS以鉴定USH2A基因中的突变。变异分析,Sanger验证,和隔离测试被用来验证这些家族的致病突变。
我们确定了21个致病突变，其中13例，包括5例与非综合征性RP相关，8例与USHII相关，以前没有报道过。在受影响的家庭中，新的变体与疾病表型分离，并且在对照受试者中不存在。总的来说,视觉障碍和视网膜病变在USHII和有USH2A突变的非综合征型RP患者之间是一致的.
这些发现为研究中国USHII和RP患者的基因型-表型关系以及阐明与USH2A突变相关的疾病的病理生理学和分子机制提供了基础。
