Analysis of Known Corneal Endothelial Dystrophy Loci in a Chinese Family With Fuchs Endothelial Dystrophy

Abstract

Abstract: : Purpose: The endothelial corneal dystrophies include Fuchs endothelial dystrophy (FECD), posterior polymorphous dystrophy (PPCD) and congenital hereditary endothelial dystrophy (CHED). The only gene identified to date for FECD is the COL8A2 gene, encoding the alpha 2 (VIII) collagen chain which is highly expressed in human corneal Descemet’s membrane. Mutations in the VSX1 homeobox gene have been identified for posterior polymorphous dystrophy (PPCD). We identified a Chinese family that segregated FECD with a dominant inheritance pattern and investigated the linkage to all known endothelial dystrophy loci (COL8A2, CHED1 and VSX1) in this family. Methods: For mutation analysis of COL8A2 and VSX1 primers were designed to cover the entire coding sequence of the gene. The coding regions were then PCR amplified and subjected to bi–directional sequencing using BigDye Terminator v3.1 chemistries and analyzed on an ABI PRISM 3100 Genetic Analyzer. Microsatellite markers analysed included novel poly (CA) markers localized proximal to the COL8A2 and VSX1 genes and markers D20S114 and D20S139 for CHED1 locus on chromosome 20p. Genotype data were entered using CYRILLIC 2.0 software, data exported to LINKAGE program and LOD scores calculated using MLINK. Results: Mutational analysis failed to identify pathogenic mutations in COL8A2 gene. Two point linkage analyses with two COL8A2 markers also showed exclusion of the COL8A2 locus (LOD score less than –2). The LOD score values calculated for markers for CHED1 and PPCD (VSX1) loci gave inconclusive results for linkage (or exclusion) to these loci. Conclusions: Exclusion of the COL8A2 locus in this family provides further evidence for genetic heterogeneity for FECD. Further linkage analysis is currently being performed for PPCD and CHED1 loci on chromosome 20p with additional markers.

Keywords: cornea: endothelium • genetics • mutations