Whole-Exome Sequencing Reveals Novel NDP Variants in X-Linked Familial Exudative Vitreoretinopathy

Eur J Ophthalmol. 2022 Nov;32(6):3220-3226. doi: 10.1177/11206721221074209. Epub 2022 Jan 17.

Abstract

Purpose: To investigate causative variants in three Chinese families affected with familial exudative vitreoretinopathy (FEVR).

Methods: Three unrelated Chinese families were recruited in this study. The three probands and their family members experienced a comprehensive age-appropriate eye examination and genetic analysis. Luciferase assay was performed to evaluate impacts of variants on Norrin/β-catenin signaling activity.

Results: Here we report two novel NDP variants associated with FEVR in three families, including c.17T>C (p.Leu6Pro) in family 1 and c.58G>A (p.Gly20Arg) in family 2 and 3. These two variants were co-segregated with the disease phenotypes within each family. In addition, both variants resulted in compromised Norrin/β-catenin signaling activity.

Conclusion: Our study identified two FEVR-associated pathogenic variants in NDP, which expanded the variant spectrum and provided information for the genetic diagnosis of FEVR.

Keywords: FEVR; NDP gene; WES; variants; wnt signaling.

MeSH terms

  • DNA Mutational Analysis
  • Exome Sequencing
  • Eye Diseases*
  • Eye Diseases, Hereditary* / diagnosis
  • Eye Diseases, Hereditary* / genetics
  • Eye Proteins / genetics
  • Familial Exudative Vitreoretinopathies
  • Humans
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Pedigree
  • Retinal Diseases* / diagnosis
  • Retinal Diseases* / genetics
  • Retinal Diseases* / pathology
  • beta Catenin / genetics

Substances

  • Eye Proteins
  • NDP protein, human
  • Nerve Tissue Proteins
  • beta Catenin