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Abstract

Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay.

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Acknowledgements

We thank the affected individuals and their families for participating in this study. This work was supported by a grant from the National Medical Research Council of Singapore (NMRC 0940/2005) and the Singapore Eye Research Institute. J.R.C. and P.M. are recipients of scientist and fellowship awards from the Alberta Heritage Foundation for Medical Research. Research in the laboratory of J.R.C. is funded by the Canadian Institutes of Health Research. We thank A. Liu and A. Barathi for assistance with dissection of human and mouse cornea.

Author information

Author notes

    • Eranga N Vithana
    • , Patricio Morgan
    •  & Periasamy Sundaresan

    These authors contributed equally to this work.

Affiliations

  1. Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751.

    • Eranga N Vithana
    • , Donald T H Tan
    • , Divya Venkataraman
    • , Victor H K Yong
    • , Anandalakshmi Venkatraman
    •  & Tin Aung
  2. Department of Ophthalmology, Yong Soo Lin School of Medicine, National University of Singapore, Singapore 117597.

    • Eranga N Vithana
    • , Donald T H Tan
    •  & Tin Aung
  3. Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.

    • Patricio Morgan
    •  & Joseph R Casey
  4. Aravind Medical Research Foundation, Madurai 625020, India.

    • Periasamy Sundaresan
    • , Boomiraj Hemadevi
    • , Muthiah Srinivasan
    •  & Venkatesh Prajna
  5. Institute of Ophthalmology, University College London, London EC 1V 9EL, UK.

    • Neil D Ebenezer
  6. Singapore National Eye Centre, Singapore 168751.

    • Donald T H Tan
    •  & Tin Aung
  7. Section of Ophthalmology and Neurosciences, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds LS9 7TF, UK.

    • Moin D Mohamed
    •  & Chris F Inglehearn
  8. Eye Department, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK.

    • Moin D Mohamed
    •  & Seema Anand
  9. Yangon Eye Hospital, 30 Natmauk Road, Yangon, Myanmar.

    • Khin O Khine
    •  & Myint Khine
  10. Department of Pathology, National University of Singapore, Singapore 117597.

    • Manuel Salto-Tellez
  11. Institute of Molecular and Cell Biology, Singapore 138673.

    • Ke Guo
  12. Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.

    • Joseph R Casey

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eranga N Vithana.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    CHED2 pedigree from Myanmar and cosegregation analysis of the R755Q mutation.

  2. 2.

    Supplementary Fig. 2

    Expression of SLC4A11.

  3. 3.

    Supplementary Fig. 3

    Physical map of CHED2 locus and SLC4A11 mutations.

  4. 4.

    Supplementary Fig. 4

    Allele sharing between CHED2 families with common mutations G464D and R755Q.

  5. 5.

    Supplementary Fig. 5

    Conservation of mutated residues of BTR1 as shown by multiple sequence alignment of human BTR1 with homologs and representative members of the human SLC4 family.

  6. 6.

    Supplementary Fig. 6

    Immunoblot for the BTR1 wild-type (WT) mutants.

  7. 7.

    Supplementary Note

  8. 8.

    Supplementary Methods

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DOI

https://doi.org/10.1038/ng1824

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