Retinal degeneration in cats (PRA-rdAc )

PRA-rdAc (rdAc = retinal degeneration in the Abyssinian cats) is an autosomal recessively inherited disease. It is a form of photoreceptor degeneration with a late onset that affects several breeds:

• Abyssinian cats (in this breed the mutation was first described)
• Somali cats
• Occicat
• American Curl
• Bengal
• Balinese
• Colorpoint Shorthair
• Cornish Rex
• Munchkin
• Oriental Shorthair
• Peterbald
• Siamese
• Singapura
• Tonkinese

In connection with this disease, a mutation in CEP290-gene has been identified. The modification of a base pair in intron 50 (IVS50 + 9T˃G) of CEP290 gene creates a donor splice site, resulting in 4-bp insertion and reading frame shift in mRNA transcript. The change in the reading frame results in creation of a stop codon and premature truncation of the protein. (Menotti- Raymond et al. 2007).

The mutation in CEP290-gene has been found in connection with relatively rare symptoms in humans, with failures of eye or kidney development, mental retardation and other clinical symptoms (such as Jourbert syndrome, Senior-Løken syndrome, Meckel-Gruber syndrome and Bardet-Biedl syndrome).

The unusual high incidence of recessively inherited degeneration of retina in Abyssinian cats was first discovered in Sweden in 1983. It has been found a high prevalence of affected animals and carriers in the population (45% and 44%). Within several years since the rdAC has been first described, the disease became more frequent and was observed in other northern countries and in the Netherlands and Germany as well.  The possible cause of such high prevalence of the disease could be excessive inbreeding (breeding between relatives) between purebred Abyssinian cats, incl. mating of parents with their offsprings.

The funduscopic exam of retina of a cat affected by rod-cone degeneration (rdAc) is still normal approximately by the age of 1.5 - 2 years. The retinal changes observed by ophthalmologic exams are then slowly progressive and lead to retinal atrophy. By ERG-examination, the retinal changes can be observed sooner, at an age of about 8 months.

Four specific stages (S1-S4), as observed ophthalmoscopically, have been described in order to correlate funduscopic changes with other clinical and laboratory findings (Narfström et al. 2009).

1. In stage 1 (S1) (the stage of suspected disease): slight color changes are observed in the central part of the fundus, most often along the visual streak.
2. In stage 2 (S2) (early disease): distinct grayish color changes are observed centrally, with additional and distinct color changes in the peripheral tapetal fundus.
3. In stage 3 (S3): generalized color changes are observed in all of the tapetal area as well as hypo- and hyperreflective areas in the midperipheral and peripheral tapetal fundus. Additionally, vascular attenuation and some minute changes in the non-tapetal fundus, such as mottling and depigmentation are observed.
4. In stage 4 (S4): generalized hyperreflectivity of the tapetal fundus are observed, as well as generalized vascular attenuation, marked depigmentation, some hyperpigmentated spots in the non-tapetal fundus and occasionally, hyporeflective areas along the visual streak. The end stage (S4) was usually reached in most affected cats between 3 and 5 years of age.

The frequency of the found mutant rdAc-allele was as follows: in Scandinavia (0.20), UK (0.21) and Australia (0.11).

The molecular-genetic testing reveals the carrier of the disease. By suitable breeding, it is possible to reduce the occurrence of the disease in the population.

PRA-rdAc is an autosomal recessive disorder. The disease affects cats with P/P (positive / positive) genotype only. Cats with P/N (positive /negative) genotype are clinically without any symptoms. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

References:

Menotti-Raymond M, VA Davis, AA Schaffer et al. Mutation in CEP290 discovered for cat model of human retinal degeneration.  Journal of Heredity 98(3):211-220 (2007).

Narfström K., David V., Jarret O., Beatty J., Barrs V., Wilkie D., O'Brien S. and Menotti-Raymond M. Retinal degeneration in the Abyssinian and Somali cat (rdAc):correlation between genotype and phenotype and rdAc allele frequency in two continents. Veterinary Ophthalmology (2009) 12, 5, 285-291