Gordon Setter & Late-Onset PRA (rcd4 / C2orf71): Why a Clear Eye Exam at Three Isn’t the Whole Story

The short answer: rcd4-PRA in the Gordon Setter is an inherited retinal disease caused by the C2orf71 (PCARE) c.3149_3150insC variant, and it is autosomal recessive — so a dog with just one copy (a carrier) stays healthy and never goes blind from rcd4. The disease is notably late-onset, with vision loss usually appearing around 5–12 years of age (mean near 10), which means a normal eye exam in a young dog does NOT clear it — the single strongest reason to test genetically. The DNA test is a genetic risk/carrier screen, not a clinical diagnosis: it detects the variant, while actual PRA is confirmed by a veterinary ophthalmologist. A clear rcd4 result does not rule out every form of PRA, because other genes can cause retinal degeneration too. The real value of testing is informed breeding and early owner preparation, not a cure.

What PRA and rcd4 are — and the C2orf71 gene behind it

SamMy brother-in-law’s Gordon Setter is going blind at 10 — is this the same “PRA” I keep reading about?

Elena MarshVery likely the rcd4 form, caused by a C2orf71 variant that Downs 2013 identified in Gordon and Irish Setters.

Progressive retinal atrophy (PRA) is not one disease but a family of inherited disorders in which the retina’s photoreceptors — the rod and cone cells that capture light — gradually die. Owners typically notice night blindness first, because rods fail earliest, followed by loss of day vision, ending in complete blindness. The process is bilateral, non-painful, and steady rather than sudden.

In the Gordon Setter, the relevant form is rod-cone dysplasia 4 (rcd4), caused by a single-cytosine insertion (c.3149_3150insC) in the C2orf71 gene, now also known as PCARE. This frameshift variant was characterised by Downs and colleagues in 2013 and is catalogued as OMIA:001575-9615. Because PRA is genetically heterogeneous — different breeds carry mutations in different genes — the specific variant matters when you choose a test.

References: Downs et al. 2013 (https://pubmed.ncbi.nlm.nih.gov/22686255/); OMIA:001575-9615 (https://omia.org/OMIA001575/9615/).

Why late onset makes genetic testing so valuable

SamMy own Gordon Setter had a clean eye exam at three — doesn’t that settle it?

Elena MarshUnfortunately no; Downs 2013 describes rcd4 as late-onset, so signs may not appear until roughly ten years of age.

The defining feature of rcd4 is its late onset. Visual impairment typically emerges somewhere between about 5 and 12 years of age, with a mean around 10 years. That timeline is precisely what makes clinical screening alone unreliable in young dogs: a fundus examination at age two or three can look entirely normal in a dog that will still go blind years later.

Genetic testing sidesteps this problem, because the C2orf71 variant is present from conception and does not depend on whether symptoms have yet appeared. For a breeder deciding which dogs to pair — or an owner wanting to plan ahead — a DNA result available in puppyhood is far more informative than an eye exam that only reflects the retina’s condition on the day it was done.

Reference: general PRA and ophthalmology context (https://pmc.ncbi.nlm.nih.gov/articles/PMC10472985/).

A genetic risk screen is not a clinical diagnosis

SamIf the DNA test comes back “affected,” does that mean my dog already has PRA?

Elena MarshIt means the genotype confers risk; the clinical disease itself is confirmed by a veterinary ophthalmologist, not by the lab result.

It is important to keep two things separate. The DNA test is a genetic risk/carrier screen: it reports whether the C2orf71 c.3149_3150insC variant is present, and in what dose. It does not measure the retina or tell you how far any degeneration has progressed. Clinical PRA — the actual disease — is diagnosed by a veterinary ophthalmologist using a dilated fundus examination and, where needed, electroretinography (ERG) to measure photoreceptor function.

The two tools complement each other. A “genetically affected” result flags a dog that is at high risk and warrants ophthalmic monitoring; the ophthalmologist then confirms and stages any visible degeneration. Commercial screening for this specific variant is offered by several laboratories, including UC Davis VGL (“PRA rcd4”), Laboklin/Labogen, and CombiBreed, and the test is OFA-listed.

Reference: UC Davis VGL PRA rcd4 (https://vgl.ucdavis.edu/test/progressive-retinal-atrophy-rcd4-pra).

Recessive genetics: clear, carrier, and affected

SamMy dog is a “carrier” — does that mean he’ll eventually lose his sight too?

Elena MarshNo; because rcd4 is recessive, a single-copy carrier stays healthy, and the concern only arises when two carriers are bred together.

rcd4 is autosomal recessive, which means a dog needs two copies of the variant to be at risk of disease. A dog with one copy — a carrier — is clinically healthy and will never go blind from rcd4, but can pass the variant to offspring. This is why carriers are perfectly usable in a breeding program, provided their mate is clear.

The genetics of a carrier-to-carrier pairing follow simple Mendelian ratios: on average one quarter of the puppies are affected, one half are carriers, and one quarter are clear. Testing lets breeders avoid ever placing two carriers together, eliminating affected puppies without shrinking the gene pool.

Reference: OMIA:001575-9615 (https://omia.org/OMIA001575/9615/).

rcd4 isn’t the only PRA — heterogeneity, cure, and supportive care

SamSo if my Gordon Setter tests clear for rcd4, I can stop worrying about blindness entirely?

Elena MarshNot quite; PRA is genetically heterogeneous, so a clear rcd4 result rules out that one variant but not every retinal disease.

A clear rcd4 result is reassuring, but it is specific to the C2orf71 variant. PRA is genetically heterogeneous, and rcd4 should not be called “the” Gordon Setter PRA — it is one recessive variant that happens to occur in the breed. rcd4 (C2orf71) is a different disease from rcd1 (a PDE6B mutation described in the Irish Setter) and from the Tibetan and Lhasa PRA genes such as FAM161A and IMPG2; these should never be conflated. Gordon Setters can also carry unrelated variants — for example RAB24-associated ataxia — so a clean rcd4 report does not clear a dog of all inherited eye or neurological disease.

There is currently no cure for rcd4-PRA, and management is supportive. Because the vision loss is gradual, most affected dogs adapt remarkably well when their owners keep the home environment consistent, avoid moving furniture, and add night lighting to help during the transition. The value of genetic testing therefore lies in informed breeding decisions and giving owners time to prepare — not in treatment.

Frequently asked questions (FAQ)

Q. My Gordon Setter passed an eye exam at age 3 — is it clear of PRA?
Not necessarily. rcd4-PRA is late-onset (often around 10 years), so a normal exam in a young dog doesn’t rule it out. A DNA test for the C2orf71 c.3149_3150insC variant is valid from birth and gives you information the eye exam can’t at that age.

Q. My dog is an rcd4 carrier — will he go blind?
No. rcd4 is autosomal recessive, so a carrier with a single copy stays healthy and will never lose vision from rcd4. The only practical concern is breeding: two carriers paired together can produce affected puppies, so simply avoid that pairing.

Q. If the DNA test says “affected,” is that a diagnosis of PRA?
It is a genetic risk result, not a clinical diagnosis. It tells you the dog carries two copies of the variant and is at high risk, but the actual disease is confirmed and staged by a veterinary ophthalmologist using a fundus exam and, if needed, electroretinography.

Q. My dog tested clear for rcd4 — is his eyesight guaranteed safe?
A clear result rules out this specific variant only. PRA is genetically heterogeneous and other genes exist, and Gordon Setters can carry unrelated conditions too, so continue routine ophthalmic checks even after a clear rcd4 result.

References

• Downs et al. 2013, Animal Genetics (Gordon/Irish Setter C2orf71 rcd4-PRA) — https://pubmed.ncbi.nlm.nih.gov/22686255/
• OMIA:001575-9615, Online Mendelian Inheritance in Animals (rcd4) — https://omia.org/OMIA001575/9615/
• UC Davis Veterinary Genetics Laboratory, PRA rcd4 test — https://vgl.ucdavis.edu/test/progressive-retinal-atrophy-rcd4-pra
• Progressive retinal atrophy and canine ophthalmology diagnosis (review) — https://pmc.ncbi.nlm.nih.gov/articles/PMC10472985/

Image: Bluesik, “Gordon Setter”, CC BY-SA 4.0, via Wikimedia Commons.

About the author

Elena Marsh

Editor & writer (not a veterinarian)

A writer with a molecular-biology background and a lifelong dog and cat owner. Not a veterinarian — she translates peer-reviewed genetics research and primary data into plain language, always as information rather than diagnosis.