Novel mutations in the TSPAN12 gene in Chinese patients with familial exudative vitreoretinopathy

	Novel mutations in the TSPAN12 gene in Chinese patients with familial exudative vitreoretinopathy
	Xu, Yu ; Huang, Lulin ; Li, Jing ; Zhang, Qi ; Fei, Ping ; Zhu, Xiong ; Tai, Zhengfu ; Ma, Shi ; Gong, Bo ; Li, Yun ; Zang, Weizhou ; Zhu, Xianjun ; Zhao, Peiquan ; Yang, Zhenglin
刊名	MOLECULAR VISION
	2014
卷号	20 期号:2014 页码:1296-1306
通讯作者	Yang, ZL (reprint author), Sichuan Acad Med Sci, Ctr Human Mol Biol & Genet, 32 First Round Rd 2 West, Chengdu 610072, Sichuan, Peoples R China.
产权排序	4
合作状况	其它
英文摘要	Purpose: Familial exudative vitreoretinopathy (FEVR) is a group of inherited blinding eye diseases characterized by defects in the development of the retinal vessels. Recent studies have identified genetic variants in tetraspanin 12 (TSPAN12) as a cause of FEVR. The purpose of this study was to identify novel TSPAN12 mutations in Chinese patients with FEVR and to describe the associated phenotypes. Methods: Mutation screening was performed by directly sequencing PCR products of genomic DNA with primers designed to amplify the seven coding exons and adjacent intronic regions of the FEVR-causing gene TSPAN12. Clinical phenotypes of the patients with TSPAN12 mutations were documented. Wild-type and mutant TSPAN12 proteins were assayed for the Norrin-beta-catenin signaling pathway with luciferase reporter assays. Results: Three novel heterozygous mutations in TSPAN12 were identified: c.566G>A (p.C189Y), c.177delC (p.Y59fsX67), and c.C254T (p.T85M). All three mutations involved highly conserved residues and were not present in 200 normal individuals. Ocular phenotypes included increased ramification of the peripheral retinal vessels, a peripheral avascular zone, inferotemporal dragging of the optic disc and macula, and retinal folds. The probands showed relatively severe retinopathy, whereas the other family members were often asymptomatic. In SuperTopFlash (STF) cell line transfection studies, C189Y, Y59fsX67, and T85M mutants failed to induce luciferase reporter activity in response to Norrin. Conclusions: We found three novel TSPAN12 mutations in Chinese patients with autosomal dominant FEVR, and suggest that TSPAN12 mutations cause FEVR. The phenotypes associated with the TSPAN12 mutations showed extensive variation in disease severity among members of the same family, which implied the complexity of FEVR mutations and phenotypes.
学科主题	Biochemistry & Molecular Biology; Ophthalmology
收录类别	SCI
语种	英语
公开日期	2016-02-26
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/26664]
专题	成都生物研究所_天然产物研究
推荐引用方式 GB/T 7714	Xu, Yu,Huang, Lulin,Li, Jing,et al. Novel mutations in the TSPAN12 gene in Chinese patients with familial exudative vitreoretinopathy[J]. MOLECULAR VISION,2014,20(2014):1296-1306.
APA	Xu, Yu.,Huang, Lulin.,Li, Jing.,Zhang, Qi.,Fei, Ping.,...&Yang, Zhenglin.(2014).Novel mutations in the TSPAN12 gene in Chinese patients with familial exudative vitreoretinopathy.MOLECULAR VISION,20(2014),1296-1306.
MLA	Xu, Yu,et al."Novel mutations in the TSPAN12 gene in Chinese patients with familial exudative vitreoretinopathy".MOLECULAR VISION 20.2014(2014):1296-1306.