UC Davis Veterinary Genetics Laboratory Discovers Genetic Cause of Another Equine Eye Disorder

An international collaboration between the UC Davis Veterinary Genetics Laboratory and The Royal (Dick) School of Veterinary Studies (R(D)SVS; Edinburgh), two leading veterinary schools, allowed for the discovery of the first known genetic cause of a rare eye condition called ectopia lentis in horses.

Ectopia lentis happens when the lens of the eye is out of place, which often leads to blindness. While it has been well documented in humans and other animals, with genetic causes known, this is the first case to be reported in the horse for which a genetic cause was identified.

This condition is something we rarely see in horses. In fact, only two previous cases have been documented to date”, says Dr.  Kristopher Houston, who was the ophthalmology resident at the Royal (Dick) School of Veterinary Studies that first investigated this case.

The 3-day-old crossbred colt presented with mild limb deformities as well as small and abnormally round lenses that were shifted downward within the eye, characteristic of ectopia lentis. Histopathological analysis was also performed confirming the colt had ectopia lentis.

Senior ophthalmologist on this case, Prof. Claudia Hartley, adds

Given the vast knowledge of genetic components of this disorder in humans, when this case was presented at our clinic with similar abnormalities in each eye, that hinted to a genetic case in horses too. That is why we reached out to Dr. Bellone at UC Davis, who has helped to solve other inherited ocular conditions in the horse”.

UC Davis VGL researchers used a whole genome sequencing approach to compare the foal’s DNA to the DNA of other healthy horses, investigating 46 candidate genes for changes in the DNA between the affected foal case and healthy horses.

In their investigation, one genetic variant stood out: a coding mutation in the FBN1 gene that dictates a change in the resulting fibrillin-1 protein from the normal amino acid alanine at position 882 to valine (p.Ala882Val). Fibrillin-1 protein is essential for normal connective tissue structure and computational analysis predicted the single building block change would be damaging to protein function. Notably, the same amino acid change is known to cause Marfan syndrome in humans, a genetic disorder that affects connective tissue and is often accompanied by ectopia lentis.

Because the parents were presumed unaffected, we hypothesized that a new, or as we call it de novo, mutation arose during the formation of this foal that led to the disorder” says Elizabeth Esdaile, VGL researcher and first author on this study.

Performing further analysis confirmed that the foal was heterozygous for the variant, having one normal copy of the gene and one copy with the mutation, while its confirmed dam, sire, and five paternal half-siblings did not possess the mutation at all, supporting the hypothesis of a dominant de novo mutation.

This study is the first to identify a variant in the FBN1 gene in the horse and link it to a disorder.

Given the hundreds of FBN1 pathogenic variants already documented in humans and the important role of fibrillin-1 in other connective tissues besides the eye, further investigation into FBN1-related Marfan-like syndromes in the equine population is warranted” noted Dr. Bellone, VGL director and senior author on this study.

Read the full publication here.