The identification of a novel missense mutation in only one of the patients implied that TCF8 does not play a significant role in the pathogenesis of FECD in this Chinese population.
The absence of pathogenic mutations identified in the COL8A1 or COL8A2 genes in affected members of 15 pedigrees with familial FECD indicates that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy.
To characterize histologically Descemet's membrane in an early-onset Fuchs corneal dystrophy (FCD) COL8A2 mutant and compare these findings with corneas from late-onset FCD and normal corneas.
Quantitative PCR using all three probes demonstrated that TCF4 mRNA is significantly upregulated in the corneal endothelium of patients with FECD, regardless of the presence of TNR expansion.
Seventy percent of FECD cases are due to an intronic CTG expansion within the TCF4 gene, resulting in accumulation of CUG repeat RNA nuclear foci in corneal endothelium.
Most cases of FECD are associated with an expanded CUG repeat within the intronic region of TCF4 and the mutant RNA has been implicated as the cause of the disease.
Identification of novel splicing patterns and differential gene expression in RE+/FECD- samples provides new insights and more relevant gene targets that may be protective against FECD disease in vulnerable patients with TCF4 CTG TNR expansions.
Association of single nucleotide polymorphisms (SNPs) and CTG trinucleotide repeat expansions in the intron of TCF4 gene to FECD has been studied across multiple ethnicities.
An antipeptide antibody raised against the C-terminus of the TCF4 poly-cysteine frame recognized RAN translation products by IF in cells transfected with CTG·CAG repeats and in FECD corneal endothelium.
FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.
Analysis of the diagnostic performance of individual markers in TCF4 and their combinations showed that the CTG18.1 repeat expansion was the best classifier for FECD (AUC = 0.84).