Novel FZD4 and LRP5 mutations in a small cohort of patients with familial exudative vitreoretinopathy (FEVR)

Ophthalmic Genet. 2021 Apr;42(2):200-203. doi: 10.1080/13816810.2020.1855664. Epub 2020 Dec 10.

Abstract

Purpose: To report novel mutations in the FZD4 and LRP5 genes, associated with familial exudative vitreoretinopathy (FEVR), and to correlate with clinical features of 7 FEVR patients.Methods: In this retrospective case series, 7 patients who had undergone genetic panel testing and carried a diagnosis of FEVR were identified. Comprehensive ophthalmic examination and direct DNA sequencing of FEVR-associated genes were performed in all patients. Identified sequence variants were analyzed in silico.Results: Eight mutations were identified amongst the 7 patients, that included 4 FZD4 mutations and 4 LRP5 mutations. Four novel mutations were identified, two in FZD4 (c.615delC, p.Y206MfsX34) and (c.964A>T, p.I322F), and two in LRP5 (c.2585A>T, p.D862V) and (c.1412 + 1 G > A, splice donor). A broad phenotypic spectrum was noted and no clear genotypic-phenotypic correlation was observed.Conclusion: These findings expand the mutation spectrum of FZD4 and LRP5.

Keywords: FEVR; FZD4; Familial exudative vitreoretinopathy; LRP5; genetic testing.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Familial Exudative Vitreoretinopathies / genetics*
  • Familial Exudative Vitreoretinopathies / pathology*
  • Female
  • Frizzled Receptors / genetics*
  • Genetic Association Studies*
  • Genetic Testing
  • Humans
  • Infant
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Retrospective Studies
  • Young Adult

Substances

  • FZD4 protein, human
  • Frizzled Receptors
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5