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Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2)

Nature Genetics volume 38, pages 755–757 (2006)Cite this article

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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Figure 1: Cell surface processing and immunolocalization of wild-type (WT) and mutant BTR1.

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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.

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Author notes

  1. Eranga N Vithana, Patricio Morgan and Periasamy Sundaresan: These authors contributed equally to this work.

Authors and 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, T6G 2H7, Alberta, 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, Yangon, 30 Natmauk Road, 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, 138673, Singapore

    Ke Guo

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

    Joseph R Casey

Authors
  1. Eranga N Vithana
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  9. Divya Venkataraman
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  10. Victor H K Yong
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  12. Anandalakshmi Venkatraman
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  13. Ke Guo
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  14. Boomiraj Hemadevi
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  15. Muthiah Srinivasan
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  16. Venkatesh Prajna
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  17. Myint Khine
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  18. Joseph R Casey
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  19. Chris F Inglehearn
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  20. Tin Aung
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Corresponding author

Correspondence to Eranga N Vithana.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

CHED2 pedigree from Myanmar and cosegregation analysis of the R755Q mutation. (PDF 107 kb)

Supplementary Fig. 2

Expression of SLC4A11. (PDF 88 kb)

Supplementary Fig. 3

Physical map of CHED2 locus and SLC4A11 mutations. (PDF 285 kb)

Supplementary Fig. 4

Allele sharing between CHED2 families with common mutations G464D and R755Q. (PDF 37 kb)

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. (PDF 37 kb)

Supplementary Fig. 6

Immunoblot for the BTR1 wild-type (WT) mutants. (PDF 149 kb)

Supplementary Note (PDF 9 kb)

Supplementary Methods (PDF 53 kb)

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Vithana, E., Morgan, P., Sundaresan, P. et al. Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2). Nat Genet 38, 755–757 (2006). https://doi.org/10.1038/ng1824

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  • DOI: https://doi.org/10.1038/ng1824

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