Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy

doi:10.1089/gtmb.2015.0322

	Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy
	Zhu, XJ (reprint author), Sichuan Prov Peoples Hosp, 32 First Ring Rd West 2, Chengdu 610072, Sichuan, Peoples R China.; Zhang, L; Yang, YM; Li, SJ; Tai, ZF; Huang, LL; Liu, YQ; Zhu, X; Di, YA; Qu, C
刊名	Genetic Testing and Molecular Biomarkers
	2016
卷号	20 期号:7 页码:346-351
DOI	10.1089/gtmb.2015.0322
产权排序	1
文献子类	Article
英文摘要	Background: Familial exudative vitreoretinopathy (FEVR, OMIM 133780) is a severe inherited retinal disorder characterized by incomplete retinal vascular development and neovascularization. At least five genes have been reported to be associated with FEVR, including NDP, LRP5, FZD4, TSPAN12, and ZNF408. Recently reported data showed that mutations in the KIF11 gene can also lead to FEVR conditions. Previous studies suggested that known mutations only explain approximately 40-60% of FEVR cases in different populations. Purpose: To investigate the causative genetic mutations in four Indian families with FEVR. Methods: Whole exome sequencing was carried out to analyze the genomic DNA samples from the four FEVR proband patients and Sanger sequencing was utilized to verify all identified polymorphisms. A luciferase assay was used to test the mutant protein activity. Results: We identified four novel LRP5 missense mutations in these FEVR families: c.C1042T (p.R348W), c.G1141A (p.D381N), c.C1870T (p.R624W), and c.A4550G (p.Y1517C). The luciferase assay demonstrated that all four of these LRP5 mutations led to significant reduction of enzymatic activity with response to NORRIN, suggesting that they are pathogenic. Conclusion: Our findings expand the mutational spectrum of FEVR in the Indian population and provide some guidelines in clinical diagnosis.
学科主题	Biochemistry & Molecular Biology ; Genetics & Heredity
资助项目	Zhu, Xianjun/0000-0002-2531-7552
语种	英语
资助机构	National Natural Science Foundation of China [81170883, 81430008, 81271007, 81470668, 81100693, 81300802] ; National Natural Science Foundation of China [81170883, 81430008, 81271007, 81470668, 81100693, 81300802] ; Department of Science and Technology of Sichuan Province [2012SZ0219, 2014SZ0169, 2015SZ0052, 2015SZ0060, 2014JQ0023, 2014FZ0122, 16CXTD0066, 2105JZ0004] ; Department of Science and Technology of Sichuan Province [2012SZ0219, 2014SZ0169, 2015SZ0052, 2015SZ0060, 2014JQ0023, 2014FZ0122, 16CXTD0066, 2105JZ0004] ; Department of Health of Sichuan Province [130145] ; Department of Health of Sichuan Province [130145] ; National Natural Science Foundation of China [81170883, 81430008, 81271007, 81470668, 81100693, 81300802] ; National Natural Science Foundation of China [81170883, 81430008, 81271007, 81470668, 81100693, 81300802] ; Department of Science and Technology of Sichuan Province [2012SZ0219, 2014SZ0169, 2015SZ0052, 2015SZ0060, 2014JQ0023, 2014FZ0122, 16CXTD0066, 2105JZ0004] ; Department of Science and Technology of Sichuan Province [2012SZ0219, 2014SZ0169, 2015SZ0052, 2015SZ0060, 2014JQ0023, 2014FZ0122, 16CXTD0066, 2105JZ0004] ; Department of Health of Sichuan Province [130145] ; Department of Health of Sichuan Province [130145]
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/28188]
专题	成都生物研究所_天然产物研究
通讯作者	Zhu, XJ (reprint author), Sichuan Prov Peoples Hosp, 32 First Ring Rd West 2, Chengdu 610072, Sichuan, Peoples R China.; Yang, ZL; Zhu, XJ (reprint author), Hosp Univ Elect Sci & Technol China, Sch Med, Sichuan Prov Key Lab Human Dis Gene Study, 32 First Ring Rd West 2, Chengdu 610072, Sichuan, Peoples R China.
推荐引用方式 GB/T 7714	Zhu, XJ ,Zhang, L,Yang, YM,et al. Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy[J]. Genetic Testing and Molecular Biomarkers,2016,20(7):346-351.
APA	Zhu, XJ .,Zhang, L.,Yang, YM.,Li, SJ.,Tai, ZF.,...&Zhu, XJ .(2016).Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy.Genetic Testing and Molecular Biomarkers,20(7),346-351.
MLA	Zhu, XJ ,et al."Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy".Genetic Testing and Molecular Biomarkers 20.7(2016):346-351.