Study of variants associated with Fuchs corneal endothelial dystrophy cases without expansion of CTG18.1 repeats

Fuchs' endothelial corneal dystrophy (FECD) is an inherited bilateral eye disease associated with a reduction in the density and functionality of the corneal endothelium. FECD is a genetic disease with autosomal-dominant inheritance. Genetic variants in the TCF4 gene have the most direct association with sporadic late-onset FECD in Caucasian patients. Association of the intronic single-nucleotide polymorphism (SNP) rs613872 in TCF4 gene with FECD was discovered in the Genome-Wide Association Study (GWAS) performed by Baratz et al. (2010; doi: 10.1056/NEJMoa1007064).The most specific genetic marker of the late-onset FECD also in TCF4 gene - the CTG18.1 expansion of trinucleotide repeats was discovered by Wieben et al. (2012; doi: 10.1371/journal.pone.0049083). Expansion of the CTG18.1 trinucleotide repeats is detected in approximately 70% of FECD patients of European descent populations and considered to be causal for FECD. Later the additional bigger GWAS on 1404 FECD cases and 2564 controls was conducted by Afshari with coauthors (2017; doi: 10.1038/ncomms14898). However, there was no information on the CTG18.1 expansion status available for the whole set of participants. Participants of our set were genotyped for CTG181.1 expansion. We used our set to mark the haplotype associated with the CTG181.1 expanded allele. The overall set included 31 sample. There are two groups divided by condition and the CTG18.1 expansion status: patients with Fuchs endothelial corneal dystrophy without CTG18.1 expansion (n = 26) and control group with CTG18.1 expansion (n = 5). All of the patients from the Fuchs endothelial corneal dystrophy group were Caucasian.