Mutations in LRP5,FZD4, TSPAN12, NDP, ZNF408, or KIF11 Genes Account for 38.7% of Chinese Patients With Familial Exudative Vitreoretinopathy

Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2623-2629. doi: 10.1167/iovs.16-21324.


Purpose: Familial exudative vitreoretinopathy (FEVR) is a severe hereditary retinal disorder characterized by defects in retinal vascular development. To date, six genes have been reported to be responsible for this disease, including LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to investigate the genetic defects in Chinese patients with FEVR through mutational analyses of 31 pedigrees.

Methods: Clinical data and peripheral blood were collected from 31 pedigrees with FEVR. All coding sequences and intron/exon junctions were amplified and sequenced comprehensively, followed by cosegregation testing to verify suspected variants in the family members. Finally, we assessed clinical relevance of the identified mutations, according to the standards and guidelines from the American College of Medical Genetics and Genomics.

Results: Twelve index cases (12/31, 38.7%) were confirmed to harbor mutations in the known genes, including one previously reported mutation and 11 novel mutations. Among the detected mutations, LRP5 accounted for the largest proportion with a mean mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31, 6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were predicted to be pathogenic by a series of bioinformatics analyses.

Conclusions: We comprehensively screened six known disease-causing genes in 31 pedigrees with FEVR and achieved a clear picture of the mutation spectrum in Chinese patients with FEVR, which highlights the importance and utility of clinical genetic diagnosis.

MeSH terms

  • China / epidemiology
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Exons
  • Eye Diseases, Hereditary
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Familial Exudative Vitreoretinopathies
  • Female
  • Frizzled Receptors / genetics*
  • Frizzled Receptors / metabolism
  • Humans
  • Incidence
  • Kinesin / genetics
  • Kinesin / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics*
  • Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
  • Male
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Pedigree
  • Phenotype
  • Retinal Diseases / epidemiology
  • Retinal Diseases / genetics*
  • Retinal Diseases / metabolism
  • Tetraspanins / genetics*
  • Tetraspanins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Eye Proteins
  • FZD4 protein, human
  • Frizzled Receptors
  • KIF11 protein, human
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • NDP protein, human
  • Nerve Tissue Proteins
  • TSPAN12 protein, human
  • Tetraspanins
  • Transcription Factors
  • ZNF408 protein, human
  • Kinesin

Supplementary concepts

  • Familial Exudative Vitreoretinopathy