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.
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。