June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Identification of CTNND1 mutations in Familial Exudative Vitreoretinopathy
Author Affiliations & Notes
  • Dong Sun
    University of Leeds Leeds Institute of Medical Research at St James's, Leeds, West Yorkshire, United Kingdom
  • Robert Henderson
    Great Ormond Street Hospital for Children NHS Foundation Trust, London, London, United Kingdom
    University College London Institute of Child Health, London, London, United Kingdom
  • Emma Clement
    Great Ormond Street Hospital for Children NHS Foundation Trust, London, London, United Kingdom
    University College London Institute of Child Health, London, London, United Kingdom
  • Genomics England Research Consortium
    United Kingdom Department of Health and Social Care, London, London, United Kingdom
  • Chris Inglehearn
    University of Leeds Leeds Institute of Medical Research at St James's, Leeds, West Yorkshire, United Kingdom
  • James A. Poulter
    University of Leeds Leeds Institute of Medical Research at St James's, Leeds, West Yorkshire, United Kingdom
  • Carmel Toomes
    University of Leeds Leeds Institute of Medical Research at St James's, Leeds, West Yorkshire, United Kingdom
  • Footnotes
    Commercial Relationships   Dong Sun None; Robert Henderson None; Emma Clement None; Genomics England Research Consortium None; Chris Inglehearn None; James Poulter None; Carmel Toomes None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4536. doi:
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      Dong Sun, Robert Henderson, Emma Clement, Genomics England Research Consortium, Chris Inglehearn, James A. Poulter, Carmel Toomes; Identification of CTNND1 mutations in Familial Exudative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4536.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Familial exudative vitreoretinopathy (FEVR) is an inherited eye disease characterised by the incomplete development of the retinal vasculature. The resulting avascularity often leads to retinal ischemia which can cause neovascularization, retinal folds and retinal detachment, leading to vision loss. Over ten genes have been associated with FEVR but there are still a substantial number of genetically unsolved cases. The aim of this study was to identify new genes underlying FEVR through analysing the whole genome sequencing (WGS) data of FEVR cases from the Genomes England (GEL) 100,000 genomes project.

Methods : WGS was performed by GEL. Genomes were aligned using Isaac and variants were called using Starling. Candidate variants were extracted from the FEVR cohort data using the ‘gene-variant workflow’ and ‘CNV/SV workflow’ and by using BCFtools in unfiltered VCF files.

Results : A cohort of 59 FEVR cases were identified in GEL. Analysis of the known FEVR genes solved 14/59 (23.73%) of these cases. Analysis of the remaining unsolved GEL cases highlighted CTNND1 as a new candidate FEVR gene as three different heterozygous variants were identified in unrelated individuals. A de novo heterozygous splice donor site variant was identified in patient 49.1 (c.1963+1G>T: p.?) (NM_001085458.2). A heterozygous missense variant c.935C>T: p.S312F was identified in singleton proband 29.1. Finally, a heterozygous missense variant c.259G>A: p.G87R was found in patient 56.1. This variant was inherited from an unaffected mother. All of the variants are rare and the missense variants were conserved and predicted to be pathogenic by multiple prediction tools.

Conclusions : We identified three UK FEVR cases with potential pathogenic variants in CTNND1 using the GEL 100,000 genome project. Recently, three different heterozygous CTNND1 variants were described in Chinese cases of FEVR (Yang et al. 2022). Our work supports a role that variants in CTNND1 underlie FEVR.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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