Fuchs corneal dystrophy, a genetic disorder that necessitates corneal transplant operations could be caused by a gene identified in a new study.
A 13-member research team led by University of Oregon scientist Dr. Albert O. Edwards performed a genome-wide analysis comparing patients with and without typical age-related Fuchs, finding an alteration in the transcription-factor-4 gene (TCF4). Fuchs -- pronounced FEWKS or FOOKS -- generally emerges in middle-aged, roughly age 40, and older people.
Fuchs emerges slowly with blurred or cloudy vision, tiny bumps known as guttae (GOO-tay) on the cornea's surface and, in severe stages, painful blisters on the corneal surface.
"It vastly exceeds the risk found previously for the complement-factor-H gene in macular degeneration," he said.
"If a person has risk variants involving TCF4, that individual is anywhere from several to a couple of hundred times more likely to have Fuchs disease."
While the TCF4 gene has been identified, exactly what occurs to cause a defect is not understood. The researchers found evidence that at least one transcription protein, E2-2, needs more scrutiny.
ZEB1, which may be regulated by E2-2, already is thought to contribute to Fuchs.
The study involved the genotyping of 280 Fuchs patients recruited in clinical settings in Minnesota and Michigan. These patients had at least Stage 1 signs of Fuchs or had received corneal replacements as a result of the disease. Their genomes were compared with 410 control patients.
Three other genes previously had been linked to very rare subtypes of Fuchs. In addition, early onset Fuchs has been linked to mutations in yet another gene, COL8A2, but Edwards and colleagues suggest in their paper that this may be a different disease with a different cause.
The discovery has been published in the New England Journal of Medicine.