TCF4 trinucleotide repeat expansion in Finnish patients with Fuchs' endothelial corneal dystrophy

Abstract

AbstractPurpose: To study the presence and role of transcription factor 4 (TCF4) triplet repeat expansion in Finnish patients with Fuchs' endothelial corneal dystrophy (FECD) which causes a progressive loss of corneal endothelial cells, resulting in loss of corneal clarity, and is the leading cause of corneal transplantations in Western countries. FECD has a heterogeneous genetic background, but the best‐known risk variant is a CTG‐repeat expansion in the TCF4 gene. An expansion of more than 40 repeats is associated with an increased risk for the disease.Methods: One hundred and twelve Finnish patients with a clinical diagnosis of FECD treated in the Helsinki University Hospital, and 202 control individuals from the Finnish Red Cross Biobank were enrolled. The patients were examined by slit‐lamp, anterior segment photography, corneal tomography, OCT, and endothelial specular microscopy. To assess the repeat number in TCF4, short tandem repeat analysis and triplet repeat primed PCR were used.Results: Of the 112 patients with FECD, 79 were female and 33 male. A CTG‐expansion of >40 was observed in 84% (95% confidence interval [CI], 76–90) of the patients of whom two had the expansion in both alleles. In contrast, only 3% (95% CI, 1–6) of the 202 control individuals had such an expansion, each of them in a heterozygous state. Of the patients with <40 vs. >4 0 CTG‐repeats 89% vs. 97% had transplantation surgery performed in at least one eye.Conclusions: These results indicate that the CTG‐repeat expansion in TCF4 is a notable risk factor for FECD also in the Finnish population with >80% of the patients carrying the expansion. Further analysis will be performed to clarify the association of the expansion with the clinical and pathological features in these patients.