CRB1-Related Cystic Maculopathy in Twins Conceived Through Heterologous Fertilization With Variant-Carrying Oocytes

J Pediatr Ophthalmol Strabismus. 2020 Mar 12;57:e19-e24. doi: 10.3928/01913913-20200204-02.


Cystic maculopathy has been associated with genetic disorders such as retinitis pigmentosa, X-linked retinoschisis, cone dystrophy, and foveal retinoschisis. Familial foveal retinoschisis was recently described as a rare disease caused by CRB1 variants. The authors report the phenotype-genotype pattern of a pair of dizygotic twins with early-onset cystic maculopathy due to CRB1 pathogenic variants. The twins were conceived by heterologous fertilization with variant-carrying oocytes. The probands were monitored for a period of 4 years. Next generation sequencing of a panel of genes responsible for retinal dystrophies was performed. Both children carried three pathogenic variants in CRB1: a novel heterozygous truncating variant p.(Val855*) inherited from the father and two known heterozygous missense variants, p.[(Phe144Val; Thr745Met)], inherited from the oocyte donor. The findings confirm that CRB1 variants can be responsible for foveal retinoschisis with variable clinical expressivity ranging from schitic macular alteration to early-onset forms of cystic maculopathy. The authors highlight the importance of exome analysis of gamete donors to assess the likelihood of recessively inherited disorders by means of a prediction algorithm able to combine parent and donor exome data. [J Pediatr Ophthalmol Strabismus. 2020;57:e19-e24.].

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Eye Proteins / genetics*
  • Female
  • Fertilization in Vitro
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation, Missense
  • Nerve Tissue Proteins / genetics*
  • Oocytes / pathology
  • Phenotype
  • Retinoschisis / genetics*
  • Twins, Dizygotic


  • CRB1 protein, human
  • Eye Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins