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M. A. Minear, N. A. Afshari, E. Balajonda, B. Zhao, J. Rimmler, Y.-J. Li, G. K. Klintworth, S. G. Gregory; Analysis of SLC4A11 and COL8A2 Mutations in Fuchs Endothelial Corneal Dystrophy (FECD). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4639.
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To determine whether previously reported mutations in COL8A2 and SLC4A11, two genes implicated in Fuchs endothelial corneal dystrophy (FECD), could be identified in a small sample of our dataset of FECD cases. We also sought to detect novel mutations in these genes that may influence FECD pathogenesis.
FECD patients were recruited through an ongoing study at the Duke University Eye Center. Fourteen individuals diagnosed with FECD before 50 years of age (early onset cases) were used for COL8A2 sequencing, and 24 individuals diagnosed after 50 years of age (late onset cases) with tissue-confirmed diagnoses were selected for SLC4A11 sequencing. All sequences were generated on a 3730XL DNA Analyzer (Applied Biosystems Inc.) and were analyzed using the program Sequencher. Unrelated control individuals (over 60 years of age) were used to verify the presence of variations detected in cases.
The p.L450W mutation in COL8A2, which has been implicated in early onset FECD, was not detected in any of our 14 early onset cases. Other reported COL8A2 mutations, including p.R155Q, p.R304Q, p.R434H, p.Q455K, p.Q455V, and p.T502M were also not detected in these 14 cases. In addition, the p.E399K, p.G709E, p.T754M, and c.99-100delTC mutations in SLC4A11 were not present in the 24 late onset cases. We identified several known synonymous polymorphisms in our cases, including rs35841184 in COL8A2 and rs34460295, rs3827075, rs38033956, rs6084312, rs62208067, and rs4128160 in SLC4A11.
We did not detect any of the previously reported FECD mutations in COL8A2 or SLC4A11 within a representative sample of our Caucasian FECD subjects. While our sample size limits our ability to draw conclusions about the role these mutations and genes play in FECD pathogenesis, our results suggest that other genetic factors may influence the development of FECD.
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