Late-Onset Photoreceptor Degeneration

Late photoreceptor degeneration is a form of retinal atrophy that occurs in advanced stages and follows an autosomal recessive inheritance pattern. The early clinical signs mainly affect the rods. The gene responsible for this condition is CEP290, which is essential for proper photoreceptor function.

Symptoms

This retinal condition presents with normal vision at birth, but changes are detected after 1.5 to 2 years of age. Morphologically, the first signs appear in the outer segments of the rods between 5 and 8 months, with disorganization and vacuoles at the base of these segments. As the disease progresses, the cones are also affected, culminating in complete degeneration of the photoreceptors and total blindness between 3 and 5 years of age.

Disease Management

Currently, there is no specific treatment to reverse or halt the progression of this condition. Management focuses on providing supportive care to improve the quality of life of the affected cat. This may involve environmental adjustments, such as adapting the home to the cat`s visual difficulties.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.

Technical report

Late photoreceptor degeneration is characterized by the progressive loss of these essential components of vision and is associated with a mutation in the CEP290 gene, which is involved in photoreceptor function and maintenance. CEP290 is a highly conserved protein in mammals, involved in the intracellular transport of proteins essential for phototransduction in the outer segments of photoreceptors. The mutation responsible, a single nucleotide substitution in an intronic region of the CEP290 gene, generates an aberrant splice site, resulting in a 4-base pair insertion and a reading frame shift in the mRNA transcript. This causes premature truncation of the CEP290 protein, affecting the ability of the primary cilium of photoreceptors to transport crucial proteins to the outer segments, which is essential for the continued regeneration of photoreceptor discs and, ultimately, vision.

Most affected breeds

Abyssinian
American Curl
American Shorthair
Balinese
Bengal
Cornish Rex
Devon Rex
Donskoy
European Shorthair
Havana
Highlander
Maine Coon
Manx
Munchkin
Ocicat
Oriental Longhair
Oriental Shorthair
Peterbald
Pixiebob Longhair
Ragdoll
Savannah
Scottish Fold
Siamese
Singapura
Somali
Sphynx
Tennessee Rex
Tonkinese

Bibliography

Menotti-Raymond M, David VA, Schäffer AA, et al. Mutation in CEP290 discovered for cat model of human retinal degeneration. J Hered. 2007 May-Jun