Zhang Xiao, Ge Xianglian, Yu Ying, Zhang Yilan, Wu Yaming, Luan Yin, Sun Ji, Qu Jia, Jin Zi-Bing, Gu Feng
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325027 China.
The Community Health Service Center in Huayuan Road, Haidian District, Beijing 10088 China.
Sci Rep. 2014 Jan 17;4:3745. doi: 10.1038/srep03745.
Idiopathic congenital nystagmus (ICN) consists of involuntary and periodic ocular motility, often with seriously reduced visual acuity. To identify the genetic defects associated with X-linked ICN, we performed PCR-based DNA direct sequencing of two candidate genes, FRMD7 and GPR143, in four families. Mutation analysis led to identification of three novel mutations, p.S260R, p.Q487X, and p.V549Y fsX554, in FRMD7 in three of the recruited families. Results from structural modeling indicated that the p.S260R may potentially disrupt FRMD7 function through loss of a phosphorylation site and/or interference with protein-protein interactions. Both p.Q487X, and p.V549Y fsX554 mutations were predicted to generate nonfunctional truncated proteins. Using a capture next generation sequencing method, we excluded CASK as the responsible gene for the remaining family. Combining sequence analysis and structural modeling, we report three novel mutations in FRMD7 in three independent families with XLICN, and provide molecular insights for future XLICN diagnosis and treatment.
特发性先天性眼球震颤（ICN）表现为不自主的周期性眼球运动，常伴有严重的视力下降。为了确定与X连锁ICN相关的基因缺陷，我们对四个家族中的两个候选基因FRMD7和GPR143进行了基于聚合酶链反应（PCR）的DNA直接测序。突变分析在三个招募的家族中发现了FRMD7的三个新突变，即p.S260R、p.Q487X和p.V549Y fsX554。结构建模结果表明，p.S260R可能通过失去磷酸化位点和/或干扰蛋白质-蛋白质相互作用而潜在地破坏FRMD7的功能。p.Q487X和p.V549Y fsX554突变均预计会产生无功能的截短蛋白。使用捕获二代测序方法，我们排除了CASK作为其余家族的致病基因。结合序列分析和结构建模，我们报告了三个独立的X连锁ICN家族中FRMD7的三个新突变，并为未来X连锁ICN的诊断和治疗提供了分子见解。
