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Mol Vis. 2017 Aug 23;23:605-613. eCollection 2017.

Targeted next-generation sequencing analysis identifies novel mutations in families with severe familial exudative vitreoretinopathy.

Huang XY1,2,3, Zhuang H4,5, Wu JH4,5, Li JK2,3, Hu FY4,5, Zheng Y1,2,3, Tellier LCAM2,3,6, Zhang SH4,5, Gao FJ4,5, Zhang JG2,3, Xu GZ4,5.

Author information

BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.
BGI-Shenzhen, Shenzhen, China.
China National GeneBank-Shenzhen, BGI-Shenzhen, Shenzhen, China.
Eye and ENT Hospital, Fudan University, Shanghai, China.
Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
Department of Biology, Bioinformatics, University of Copenhagen, Denmark.



Familial exudative vitreoretinopathy (FEVR) is a genetically and clinically heterogeneous disease, characterized by failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. This study was designed to identify the genetic defect in a patient cohort of ten Chinese families with a definitive diagnosis of FEVR.


To identify the causative gene, next-generation sequencing (NGS)-based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members by using Sanger sequencing and quantitative real-time PCR (QPCR).


Of the cohort of ten FEVR families, six pathogenic variants were identified, including four novel and two known heterozygous mutations. Of the variants identified, four were missense variants, and two were novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del]. The two novel heterozygous deletion mutations were not observed in the control subjects and could give rise to a relatively severe FEVR phenotype, which could be explained by the protein function prediction.


We identified two novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del] using targeted NGS as a causative mutation for FEVR. These genetic deletion variations exhibit a severe form of FEVR, with tractional retinal detachments compared with other known point mutations. The data further enrich the mutation spectrum of FEVR and enhance our understanding of genotype-phenotype correlations to provide useful information for disease diagnosis, prognosis, and effective genetic counseling.

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