Whole-Exome Sequencing Analysis Identified Novel Mutations in the TSPAN12 Gene in Chinese Families with Familial Exudative Vitreoretinopathy
Whole-Exome Sequencing Analysis Identified Novel Mutations in the TSPAN12 Gene in Chinese Families with Familial Exudative Vitreoretinopathy
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DOI：
10.1089/gtmb.2019.0049
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发表时间：
2019
影响因子：
1.4
通讯作者：
Yang Zhenglin
中科院分区：
文献类型：
--
作者：
Yuan Ye;Xu Huijuan;Zhang Shanshan;Zhang Xiang;Zhang Lin;Yang Zhenglin
背景：家族性渗出性玻璃体视网膜病变(FEVR，OMIM 133780)是一种严重的遗传性视网膜疾病，以视网膜血管发育不全和病理性新生血管为特征。已有10个基因的突变被报道与胎儿宫内发育迟缓有关，但仍有50%的胎儿宫内发育迟缓病例仍有待遗传学解释。目的：本研究的目的是鉴定新的致病基因突变，探索中国胎儿宫内发育迟缓家系的致病突变。方法：采用全外显子组测序的方法对12 1个胎儿宫内发育迟缓先证者的基因组∼进行分析。进行Sanger测序以验证所有已鉴定的突变。结果：在这些家系中发现了4个新的杂合子TSPAN12(β12)突变，包括2个单碱基替换突变和2个小缺失突变：C.1a>；G(p.0)，c.614G>；A(p.G205D)、c.695delT(p.V232Gfs*7)和c.833_842del(p.L278Qfs*25)。结论：本研究揭示了4个中国人FEVR家系的致病突变，发现了4个新的FEVR突变，从而扩大了FEVR在中国人群中的突变谱。
Background:Familial exudative vitreoretinopathy (FEVR, OMIM 133780), characterized by incomplete retinal vascular development and pathological neovascularization, is a severe inherited retinal disorder. Mutations in 10 genes have been reported to be associated with FEVR, but this still leaves ∼50% of FEVR cases to be genetically explained.Purpose:The purpose of this study was to identify novel FEVR-causing mutations and explore the causative mutations in Chinese FEVR families.Methods:Whole-exome sequencing was performed to analyze the genomic DNA of the probands from 121 Chinese FEVR families. Sanger sequencing was carried out to verify all identified mutations. Luciferase assays were used to test the activity of a mutant protein in the Norrin-β-catenin signaling pathway.Results:Four novel heterozygousTSPAN12(Tetraspanin 12) mutations, including two single-base substitution mutations and two small-deletion mutations, were identified in these FEVR families: c.1A>G (p.0), c.614G>A (p.G205D), c.695delT (p.V232Gfs*7), and c.833_842del (p.L278Qfs*25).Conclusion:This study revealed the causative mutations in four Chinese FEVR families and identified four novel FEVR-causing mutations, thus expanding the mutation spectrum of FEVR in the Chinese population.