A recurrent splice-site mutation in EPHA2 causing congenital posterior nuclear cataract

Ophthalmic Genet. 2018 Apr;39(2):236-241. doi: 10.1080/13816810.2017.1381977. Epub 2017 Oct 17.

Abstract

Intoduction: Inherited cataract, opacification of the lens, is the most common worldwide cause of blindness in children. We aimed to identify the genetic cause of autosomal dominant (AD) posterior nuclear cataract in a four generation British family.

Methods: Whole genome sequence (WGS) was performed on two affected and one unaffected individual of the family and further validated by direct sequencing. Haplotype analysis was performed via genotying.

Results: A splice-site mutation c.2826-9G>A in the gene EPHA2, encoding EPH receptor A2 was identified and found to co-segregate with disease.

Conclusions: We have identified a recurrent splice-site mutation c.2826-9G>A in EPHA2 causing isolated posterior nuclear cataract, providing evidence of further phenotypic heterogeneity associated with this variant.

Keywords: Congenital cataract; EPHA2; whole genome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cataract / congenital*
  • Cataract / genetics
  • Child
  • Chromosomes, Human, Pair 1 / genetics
  • DNA Primers / chemistry
  • Ephrin-A2 / genetics*
  • Female
  • Haplotypes
  • Humans
  • Lens, Crystalline / pathology
  • Male
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • RNA Splice Sites / genetics*
  • Receptor, EphA2
  • Recurrence
  • Whole Genome Sequencing

Substances

  • DNA Primers
  • EPHA2 protein, human
  • Ephrin-A2
  • RNA Splice Sites
  • Receptor, EphA2

Supplementary concepts

  • Cataract, Autosomal Dominant Nuclear