2. Academic Validation
  3. Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian Families with Familial Exudative Vitreoretinopathy

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

  • Genet Test Mol Biomarkers. 2016 Jul;20(7):346-51. doi: 10.1089/gtmb.2015.0322.
Lin Zhang 1 2 3,  Yeming Yang 2 3 4,  Shujin Li 1 2 3,  Zhengfu Tai 1 2 3,  Lulin Huang 2 3 4,  Yuqing Liu 2 3 4,  Xiong Zhu 1 2 3 4,  Yanan Di 2 3,  Chao Qu 2 3,  Zhilin Jiang 2 3,  Yuanfeng Li 2 3,  Guolin Zhang 1 3,  Ramasamy Kim 5,  Periasamy Sundaresan 6,  Zhenglin Yang 1 2 3 4,  Xianjun Zhu 2 3 4 7
Affiliations

Affiliations

  • 1 1 Chengdu Institute of Biology, Chinese Academy of Sciences , Chengdu, China .
  • 2 2 Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Hospital of the University of Electronic Science and Technology of China , and Sichuan Provincial People's Hospital, Chengdu, China .
  • 3 3 Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital , Chengdu, Sichuan, China .
  • 4 4 Key Laboratory for NeuroInformation of Ministry of Education and Medical Information Center, School of Medicine, University of Electronic Science and Technology of China , Chengdu, Sichuan, China .
  • 5 5 Retina-Vitreous Services, Aravind Eye Hospital , Madurai, Tamil Nadu, India .
  • 6 6 Department of Genetics, Aravind Medical Research Foundation, Aravind Eye Hospital , Madurai, Tamil Nadu, India .
  • 7 7 Institute of Laboratory Animal Sciences, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital , Chengdu, Sichuan, China .
PMID: 27228167 DOI: 10.1089/gtmb.2015.0322
Abstract

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.

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