Missense mutations in the sodium borate cotransporter SLC4A11 cause late-onset Fuchs corneal dystrophya

S. Amer Riazuddin, Eranga N. Vithana, Li Fong Seet, Yangjian Liu, Amr Al-Saif, Li Wei Koh, Yee Meng Heng, Tin Aung, Danielle N. Meadows, Allen O. Eghrari, John D. Gottsch, Nicholas Katsanis

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Homozygous mutations in the Borate Cotransporter SLC4A11 cause two early-onset corneal dystrophies: congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome. More recently, four sporadic patients with late-onset Fuchs corneal dystrophy (FCD), a common age-related disorder, were also reported to harbor heterozygous mutations at this locus. We therefore tested the hypothesis that SLC4A11 contributes to FCD and asked whether mutations in SLC4A11 are responsible for familial cases of late-onset FCD. We sequenced SLC4A11 in 192 sporadic and small nuclear late-onset FCD families and found seven heterozygous missense novel variations that were absent from ethnically matched controls. Familial data available for one of these mutations showed segregation under a dominant model in a three-generational family. In silico analyses suggested that most of these substitutions are intolerant, whereas biochemical studies of the mutant protein indicated that these alleles impact the localization and/or posttranslational modification of the protein. These results suggest that heterozygous mutations in SLC4A11 are modest contributors to the pathogenesis of adult FCD, suggesting a causality continuum between FCD and CHED. Taken together with a recent model between FCD and yet another early onset corneal dystrophy, PPCD, our data suggest a shared pathomechanism and genetic overlap across several corneal dystrophies.

Original languageEnglish (US)
Pages (from-to)1261-1268
Number of pages8
JournalHuman mutation
Issue number11
StatePublished - Nov 2010


  • Anterior segment
  • Corneal endothelium
  • Fuchs corneal dystrophy
  • SLC4A11

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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