Retinal atrophy, progressive (PRA), GUCY2D-linked

Gene: GUCY2D

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Insertion, GUCY2D gene; c.1598_1599insT, p.(Ser534Glu frameshift STOP 20), exon7, chromosome 5.

Breed: German Spitz

Medical system: Ocular

Age of onset of symptoms: 2 to 3 months.

Progressive retinal atrophy (PRA) is a family of genetic diseases that affect the vision of many dog breeds.   This can present as early onset PRA in the immature animal due to altered retinal development, or late onset PRA in the mature animal due to retinal degeneration.  When the retinal photoreceptor rod cells are affected, then impaired vision in low light intensity (night blindness) results; when retinal photoreceptor cone cells are affected, then daytime color vision is compromised.  Vision loss is progressive, often starting with loss of night vision followed by loss of day vision, as in rod-cone PRAs.  Vision loss can also follow a reversed progression, as in cone-rod PRAs.

Early onset PRA was diagnosed in a cohort of German Spitz dogs and followed a rod-cone progression pattern.  Initial signs of vision loss were observed by 2 to 3 months of age, including lack of a menace reflex, failure to avoid objects and difficulty with visual tracking.  Evidence of retinal degenerative changes were observed by 4 to 5 months of age.  Genome sequencing was performed in four dogs, and a causal mutation in the GUCY2D gene was identified.  Pedigree analysis of three pedigrees confirmed autosomal recessive heredity, whereby affected homozygous offspring had non affected heterozygous parents.  The GUCY2D gene codes for a retinal specific membrane bound enzyme found in photoreceptor cells that is involved in the process of converting environmental light energy into cellular electrical-chemical energy.

Further DNA studies of German Spitz animals are now required to determine mutation penetration and frequency rates in the breed.  In the meantime, veterinarians and breeders of German Spitz dogs should be aware of this mutation and should use DNA tests to identify carrier animals and selective breeding to eliminate this potential source of PRA in their animals.

References:

OMIA link: [2646-9615]

Bortolini M, Winkler PA, Moreno JCD, et al. (2023) Preliminary characterization of a novel form of progressive retinal atrophy in the German Spitz dog associated with a frameshift mutation in GUCY2D. Vet Ophthalmol 26:532-547.  [pm/36872573]

Genetics Committee of the American College of Veterinary Ophthalmologists (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Kelawala DN, Patil DB, Parikh PV et al. (2017) Clinical studies on progressive retinal atrophy in 31 dogs.  Iran J Vet Res. 18(2):119-123.  [pm/28775752]

Contributed by: Simon Destrempes and Anthony Racette, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)