Mutation Spectrum of the LRP5, NDP, and TSPAN12 Genes in Chinese Patients With Familial Exudative Vitreoretinopathy

Invest Ophthalmol Vis Sci. 2017 Nov 1;58(13):5949-5957. doi: 10.1167/iovs.17-22577.


Purpose: LRP5, NDP, and TSPAN12 are known to be associated with familial exudative vitreoretinopathy (FEVR). In this study, a comprehensive mutation screening for the three genes was performed in patients with a clinical diagnosis of FEVR in Han Chinese.

Methods: Genomic DNA and clinical data were collected from 100 probands and their family members. Sanger sequencing was performed to screen for LRP5, NDP, and TSPAN12 mutations and phenotype-genotype correlation was analyzed.

Results: There were 23 causative mutations identified in 23 unrelated probands (10/23 in LRP5, 8/23 in TSPAN12, and 5/23 in NDP). Apart from NDP mutations, only two LRP5 mutations inherited in an autosomal recessive manner. Among the 23 causative mutations, 13 were novel variants (4/10 in LRP5, 6/8 in TSPAN12, and 3/5 in NDP). According to the modified classification system, statistical significance was observed in the distribution of mutated genes (P = 0.049). None of the causative mutations was found in group I FEVR. Probands with LRP5 or NDP mutations were mainly categorized into group III and IV, TSPAN12 mutations were mainly observed in probands with group IV and V FEVR.

Conclusions: The detection rate for mutations in the three known genes was 23%. Mutations in LRP5 and TSPAN12 were more frequent, accounting for 10% and 8%, respectively. The NDP mutations were only identified in 6% in this cohort. There were 13 novel variants found, which provided a deeper understanding of this disease. Potential phenotype-genotype correlation was observed in the modified system. TSPAN12 mutations might lead to the most severe phenotype.

MeSH terms

  • China / epidemiology
  • DNA / genetics*
  • DNA Mutational Analysis
  • Eye Diseases, Hereditary
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Familial Exudative Vitreoretinopathies
  • Female
  • Genetic Association Studies
  • Humans
  • Incidence
  • 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


  • Eye Proteins
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • NDP protein, human
  • Nerve Tissue Proteins
  • TSPAN12 protein, human
  • Tetraspanins
  • DNA

Supplementary concepts

  • Familial Exudative Vitreoretinopathy