New study identifies major genetic risk factors behind Fuchs corneal dystrophy in Finland
A new Finnish study has provided important insights into the genetic background of Fuchs endothelial corneal dystrophy (FECD), a common age-related corneal disease that can gradually impair vision and eventually require corneal transplantation.
FECD affects the innermost layer of the cornea, called the corneal endothelium, which is responsible for keeping the cornea clear. As the disease progresses, the endothelial cells gradually deteriorate, leading to corneal swelling, blurred vision, glare, and reduced visual quality. In advanced stages, many patients require corneal transplantation surgery.
In this study, researchers investigated the genetic causes of FECD in Finnish patients using both hospital-based patient cohorts and large-scale Finnish biobank data. The researchers analyzed 107 Finnish patients with FECD and additionally performed a genome-wide association study using FinnGen data from 892 patients and nearly 500,000 controls.
The study confirmed that an expanded CTG repeat in the TCF4 gene is the major genetic risk factor for FECD, also in the Finnish population. Overall, 83% of Finnish patients with FECD carried this repeat expansion. The researchers also identified a nearby genetic marker that strongly correlates with the repeat expansion and may serve as a simpler surrogate marker in future genetic studies and potentially clinical testing.
Interestingly, patients who did not carry the TCF4 repeat expansion developed severe disease at a younger age and underwent corneal transplantation earlier than those carrying the expansion. This suggests that additional genetic mechanisms may contribute to FECD in some patients. The researchers also searched for other possible disease-causing genetic variants among patients lacking the TCF4 repeat expansion. In one patient, they identified a rare variant in the AGBL1 gene, which has previously been linked to FECD.
The findings improve understanding of the genetic architecture of FECD in Finland and further support the central role of TCF4 repeat expansions in the disease. At the same time, the study highlights that not all diseases can be explained by the known repeat expansion alone, emphasizing the need for continued research into additional genetic causes. A better understanding of the genetics behind FECD may eventually help improve diagnostics, risk prediction, and future development of targeted therapies.
Original article:
Genetic risk factors in Finnish patients with Fuchs endothelial corneal dystrophy.
Vähämäki I-T, Immonen AT, Rämö J, Jaakkola AM, Krootila K, Kaukonen M, Palotie A, Lohi H, Kivelä TT, Turunen JA. Acta Ophthalmologica. 2026.
