September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The mutational spectrum of anterior corneal dystrophies in the UK
Author Affiliations & Notes
  • Cerys J Evans
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Alice E Davidson
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Nicole Carnt
    Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia
    Moorfields Eye Hospital, London, United Kingdom
  • Neyme Veli
    Moorfields Eye Hospital, London, United Kingdom
  • Stephen J Tuft
    Moorfields Eye Hospital, London, United Kingdom
  • Alison J Hardcastle
    Institute of Ophthalmology, UCL, London, United Kingdom
  • Footnotes
    Commercial Relationships   Cerys Evans, None; Alice Davidson, None; Nicole Carnt, None; Neyme Veli, None; Stephen Tuft, None; Alison Hardcastle, None
  • Footnotes
    Support  Fight for Sight, Moorfields Eye Charity, National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4824. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Cerys J Evans, Alice E Davidson, Nicole Carnt, Neyme Veli, Stephen J Tuft, Alison J Hardcastle; The mutational spectrum of anterior corneal dystrophies in the UK. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4824.

      Download citation file:

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

  • Supplements

Purpose : Corneal dystrophies are bilateral, inherited disorders that cause corneal opacity and result in visual impairment. The majority of dystrophies that affect the anterior cornea are caused by mutations in TGFBI. We sought to identify the spectrum of mutations causing anterior corneal dystrophies in a large UK cohort of mixed ethnicity.

Methods : Individuals clinically diagnosed with an epithelial, sub-epithelial, or stromal corneal dystrophy were recruited at Moorfields Eye Hospital, London. Each proband was clinically examined and provided a blood sample for DNA extraction. Depending on the phenotype, we screened the corneal dystrophy genes TGFBI, UBIAD1 or CHST6 by direct sequencing. Mutations upstream of CHST6, previously identified to be disease causing, were screened using a PCR based assay. If the proband was mutation negative, GSN sequencing and/or plasma electrophoresis was performed. Segregation analysis was undertaken when familial samples were available.

Results : In 68 of 72 probands we identified nine different, previously reported, TGFBI mutations causing Reis-Bücklers, Thiel-Behnke, lattice or granular corneal dystrophy. Of the four probands who were TGFBI-mutation negative; two were subsequently identified to have mutations in GSN, resulting in a diagnosis of Meretoja Syndrome, and two had paraproteinaemic keratopathy confirmed by plasma electrophoresis. Interestingly, two probands with epithelial basement membrane dystrophy (EBMD) were also found to carry a mutation in TGFBI. There were 20 probands with macular corneal dystrophy; the majority had different homozygous or compound heterozygous mutations in CHST6, although p.(Leu200Arg) was found in multiple probands. Three previously reported mutations were identified in four probands with Schnyder corneal dystrophy.

Conclusions : In this large multi-ethnic cohort a limited spectrum of only nine mutations was responsible for all TGFBI-associated disease. Genotype-phenotype correlation was observed for all TGFBI mutations except p.(Gly623Asp), which was associated with a broad phenotypic spectrum; including clinical features of lattice corneal dystrophy, Reis-Bücklers dystrophy or EBMD. We have expanded the mutational spectrum of CHST6 with the identification of five novel mutations.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.