Progressive Retinal Atrophy (KIF3B gene)

Progressive retinal atrophy is an autosomal recessively inherited genetic disease that causes gradual degeneration of the retina. It initially manifests as night blindness and can lead to complete loss of daytime vision. The KIF3B gene, implicated in this condition, is involved in the assembly and maintenance of the cilia essential for the proper functioning of photoreceptors.

Symptoms

Clinical signs manifest early, with retinal degeneration observed as early as 9 weeks of age. Photoreceptor loss begins at 7 weeks with degeneration of the rods, responsible for night vision, followed by degeneration of the cones, responsible for day vision, at 9 weeks. Other symptoms include an increased tapetal reflex and a decreased ability to detect subtle movements.

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

Progressive retinal atrophy, also known as progressive Bengal retinal degeneration, is associated with mutations in the KIF3B gene. This gene encodes the KIF3B subunit of molecular motors belonging to the Kinesin-2 family, which play a crucial role in intraflagellar anterograde transport (IFT) within ciliary cells, necessary for normal cilia function. Pathogenic mutations in KIF3B, such as the c.1000G>A variant observed in Bengal cats, affect critical domains of the gene involved in abnormal primary cilia elongation and protein transport dysfunction. This leads directly to progressive retinal degeneration. These mutations compromise the structure and function of photoreceptors, which manifests clinically as retinal degeneration.

Most affected breeds

Bengal
Highlander
Highlander Shorthair
Savannah

Bibliography

Cogné B, Latypova X, Senaratne LDS, et al. Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. Am J Hum Genet. 2020 Jun 4