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S. A. Riazuddin, A. Al-Saif, L. Davey, A. Eghrari, N. Meadows, N. Katsanis, J. Gottsch; Mutations in SLC4A11 Implicated in Fuchs Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5509.
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Fuchs Endothelial Corneal Dystrophy (FECD) is the most common inheritable disorder of the corneal endothelium. It is a slow progressive disease that affects roughly 4% of the population above the age of 40, characterized clinically by the proliferation of guttae, microscopic protrusions of the collagen-rich extracellular matrix that supports the corneal endothelium. The expression levels of SLC4A11 have shown to be significantly reduced in patients diagnosed with FECD. Recent studies have potentially implicated SLC4A11 in the etiopathology of FECD. This study was undertaken to further understand the genetic basis of FECD and its underlying cellular etiology
Initially, we ascertained a cohort of 200 sporadic cases of FECD. Individuals having a Fuchs Krachmer grading of 1 (12 or more guttae in at least one eye) or higher were considered affected. We sequenced all coding exons along with the exon-intron boundaries of SLC4A11 for pathogenic mutations in our cohort
We found 8 heterozygous missense mutations that were not present in 96 ethnically matched controls. Insilco analysis suggested that these amino acid residues are conserved in other SLC4A11 orthologs.
Significant reduction of SLC4A11 expression levels in FECD patients, absence of these mutations in ethnically matched controls and conservation of these amino acids in SLC4A11 orthologs suggest that these mutations are responsible for the disease phenotype. Currently, we are investigating the significance of these mutations in an appropriate physiological system to explore the relevance of SLC4A11 dysfunction in corneal endothelium homeostasis.
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