Potential genetic cause of blindness in canines identified

The School of Veterinary Medicine at the University of Pennsylvania (Penn Vet) and the University of Padova in Padova, Italy, in collaboration with a foundation breeding service dogs for those who are visually impaired, identified a novel variant associated with progressive retinal atrophy in 3 Labrador retrievers.

The findings were recently published in Scientific Reports, and state that a genetic mutation was found in 3 of the 6 littermates affected by progressive retinal atrophy, 2 males and 1 female. The 3 patients were brought to the attention of 2 Penn Vet doctors, Leonardo Murgiano, PhD, and Gustavo D. Aguirre, VMD, PhD, DACVO, as well as their collaborators by a foundation that breeds service dogs for visually impaired human patients. Besides these 3 cases, no other dogs within the breeding program were reported to present with comparable vision deficits or retinal abnormalities.

“We have been providing services to guide dog organizations since 1989,” explained Aguirre, in an organizational release.¹ “When these organizations reach out to us, our aim is to find the mutation and develop a diagnostic test for it so that they can use it to breed dogs without this condition in the future.”

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According to the study, researchers identified a 3-bp deletion in the coding region of GTPBP2, a gene that encodes a G-protein expressed in several tissues—which includes the canine retina.² The deletion was then linked to the loss of a highly conserved alanine outside of the GTPase domain of GTPBP2, where the protein’s activity is regulated, "toggling it on and off." This indicates that the loss of this alanine affects a different aspect of the protein, potentially the cellular localization.²

An analysis of 569 Labrador retrievers from the general population of the United States as well as 91 non-affected Labrador retrievers from the same kennel was conducted and identified 16 carriers, all from the original kennel. All of the other canines were wild-type, as in they carried the "normal" version of the gene, emphasizing this variant’s rarity.

When it comes to humans, this gene mutation has been reported, but the GTPBP2 genetic variants are typically associated with Jaberi-Elahi syndrome, an extremely rare genetic disease.³ The human patients with the mutations normally present with neurologic and morphologic abnormalities as well as intellectual disabilities. For the canine patients, unlike humans with the same mutation, they presented with no other symptoms other than retinal degeneration/blindness.

“What we report here is a variant that appears to be less severe in our dogs than what is reported in humans, possibly occurring in a different region of the protein—closer to its terminal part,” Murgiano concluded.

“We have observed this before in genes attributed to syndromes—not all mutations in those genes lead to syndromes. Phenotypes can be flexible, and what we report here is an example of a flexible phenotype. This could have relevance in a general medical genetics landscape.”

References

1. New genetic cause of blindness in dogs. News release. Penn Today. March 20, 2025. Accessed March 25, 2025. https://penntoday.upenn.edu/news/penn-vet-new-genetic-cause-blindness-dogs?utm_content=Staff&utm_source=Penn+Today+-+Newsletters&utm_campaign=99fe552859-3/21/25:+Inherited+blindness&utm_medium=email&utm_term=0_-07fd5831a9-45832012
2. Murgiano L, Niggel JK, Eylem Emek Akyürek, Sacchetto R, Aguirre GD. GTPBP2 in-frame deletion in canine model with non-syndromic progressive retinal atrophy. Scientific Reports. 2025;15(1). doi:https://doi.org/10.1038/s41598-025-89446-7
3. Manoochehri J, Shiri A, Khoddam S, et al. Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review. European Journal of Medical Genetics. 2024;70:104953. doi:https://doi.org/10.1016/j.ejmg.2024.104953