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


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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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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Correspondence to Eranga N Vithana.

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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).

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