May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Identification and Characterization of SLC4A11 Mutations in Fuchs Endothelial Corneal Dystrophy (FECD)
Author Affiliations & Notes
  • E. N. Vithana
    Singapore Eye Research Institute, Singapore, Singapore
    Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • V. H. K. Yong
    Singapore Eye Research Institute, Singapore, Singapore
  • P. Morgan
    Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
  • V. Ramprasad
    ONGC Department of Genetics & Molecular biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • S. Nagasamy
    ONGC Department of Genetics & Molecular biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • G. Kumaramanickevel
    ONGC Department of Genetics & Molecular biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • J. R. Casey
    Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
  • D. T. H. Tan
    Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore
  • C. P. Pang
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • T. Aung
    Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore
  • Footnotes
    Commercial Relationships E.N. Vithana, None; V.H.K. Yong, None; P. Morgan, None; V. Ramprasad, None; S. Nagasamy, None; G. Kumaramanickevel, None; J.R. Casey, None; D.T.H. Tan, None; C.P. Pang, None; T. Aung, None.
  • Footnotes
    Support Singapore Eye Research Institute,National Medical Research Council (NMRC- 0940/2005)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1329. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      E. N. Vithana, V. H. K. Yong, P. Morgan, V. Ramprasad, S. Nagasamy, G. Kumaramanickevel, J. R. Casey, D. T. H. Tan, C. P. Pang, T. Aung; Identification and Characterization of SLC4A11 Mutations in Fuchs Endothelial Corneal Dystrophy (FECD). Invest. Ophthalmol. Vis. Sci. 2007;48(13):1329. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: The endothelial (posterior) corneal dystrophies, which result from primary endothelial dysfunction, include Fuchs endothelial dystrophy (FECD), posterior polymorphism dystrophy (PPCD) and congenital hereditary endothelial dystrophy (CHED). As they share common features of disease it is possible that a proportion of them could be clinical manifestations of different mutations of the same gene. Accordingly, mutations in COL8A2 gene which encodes the alpha 2 (VIII) collagen chain have been identified in both familial and sporadic FECD as well as in a family with PPCD. The aim of our work was to determine whether mutations in the SLC4A11 gene, recently implicated in recessive CHED may also play a pathogenic role in the development of the more common Fuchs corneal endothelial dystrophy.

Methods:: Exons 1-19 of SLC4A11 gene was PCR amplified in 90 FECD cases (64 Chinese and 25 Indian) and then subject to bi-directional sequencing. Eighty Chinese and 30 Indian samples were used as normal age matched controls. Wild type and mutant cDNA constructs were transfected in to HEK293 cells and protein extracts used for immunoblot analysis and cell surface processing assays. Confocal immunolocalization were also performed using established protocols.

Results:: Four heterozygous mutations absent in ethnically matched controls were identified in this screen of 89 FECD patients. These were three missense mutations (E399K, G709E and T754M) and one deletion mutation (99-100delTC). In addition, several silent mutations and conservative amino acid substitutions present in both FECD patients and controls were also identified. Missense mutations involved amino acid residues showing high interspecies conservation indicating that mutations at these sites would be deleterious. Accordingly, immunoblot analysis, biochemical assay of cell surface localization and confocal immunolocalization showed that missense mutants were defective in localization to the cell surface.

Conclusions:: SLC4A11 may therefore play a role in the pathogenesis of FECD through haploinsufficiency.

Keywords: gene screening • mutations • cornea: basic science 
×
×

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.

×