June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Genome wide analysis of enucleated Coats eyes
Author Affiliations & Notes
  • Denisa Dzulova
    University of Leeds, Leeds, United Kingdom
  • Carla Sanjurjo Soriano
    University of Leeds, Leeds, United Kingdom
  • James A. Poulter
    University of Leeds, Leeds, United Kingdom
  • Ian M. Carr
    University of Leeds, Leeds, United Kingdom
  • Waleed Abed Alnabi
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Nutsuchar Wangtiraumnuay
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Ralph Eagle
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Carol L Shields
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Alex V Levin
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
    Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Carmel Toomes
    University of Leeds, Leeds, United Kingdom
  • Footnotes
    Commercial Relationships   Denisa Dzulova, None; Carla Sanjurjo Soriano, None; James A. Poulter, None; Ian M. Carr, None; Waleed Abed Alnabi, None; Nutsuchar Wangtiraumnuay, None; Ralph Eagle, None; Carol Shields, None; Alex Levin, None; Carmel Toomes, None
  • Footnotes
    Support  Fight for Sight (1493/94)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2783. doi:
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    • Get Citation

      Denisa Dzulova, Carla Sanjurjo Soriano, James A. Poulter, Ian M. Carr, Waleed Abed Alnabi, Nutsuchar Wangtiraumnuay, Ralph Eagle, Carol L Shields, Alex V Levin, Carmel Toomes; Genome wide analysis of enucleated Coats eyes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2783.

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

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Abstract

Purpose : Coats disease is an idiopathic, non-hereditary retinal vasculopathy. Clinically it is characterised by retinal telangiectasia accompanied by intraretinal exudation that often progresses to exudative retinal detachment. Patients usually present with unilateral disease and the majority are young males. The Coats phenotype shares some features with familial exudative vitreoretinopathy (FEVR), a Mendelian disorder frequently associated with mutations affecting the norrin-β-catenin signaling pathway. Previously, somatic mutations in NDP, the gene encoding norrin, have been identified in Coats disease but these only account for a small proportion of cases. The purpose of this study was to use whole-exome sequencing (WES) to analyse the DNA of 7 enucleated Coats eyes to discover new genes underlying this disorder

Methods : DNA was extracted from formalin-fixed, paraffin-embedded eyes using the QIAamp DNA FFPE Tissue Kit. WES was performed on the Illumina HiSeq3000 using the Agilent SureSelect capture reagent. Data was aligned using Burrows-Wheeler Aligner (BWA) and variants were processed using Picard and Genome Analysis Toolkit (GATK). A cell based-luciferase reporter assay for β-catenin transcription (TOPflash) was used to determine the pathogenicity of the LRP5 variant.

Results : A novel heterozygous missense mutation in LRP5 was found in one eye, c.2951A>G; p.(Tyr984Cys). The variant is rare and pathogenicity prediction scores suggest that it is deleterious. LRP5 encodes a receptor for the norrin-β-catenin pathway and heterozygous germline mutations cause FEVR. A cell based-luciferase reporter assay for β-catenin transcription (TOPflash) showed that this LRP5 missense variant results in significantly reduced levels of transcription compared to wild-type LRP5 (p= ≤ 0.05).

Conclusions : This is the first report of an LRP5 mutation in Coats disease, providing further evidence that Coats is caused by defects in the norrin-β-catenin pathway and may be a somatic form of FEVR. More detailed analysis of the sequencing data is currently underway to identify mutations in the remaining eyes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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