Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 603754 (gene) , 618955 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Progressive, non-inflammatory degeneration or dysplasia of rods and cones or just of rods, leading to firstly night blindness, and later to blindness during the day.

Species-specific name: inherited retinal dystrophic or degenerative disorders; early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; Bengal progressive retinal degeneration

Species-specific description: This is an interesting example of where mapping and sequence knowledge in the cat provided sufficient information to enable human geneticists to identify two likely causal variants in humans.

Inheritance: Ofri et al. (2015): "Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats."

Mapping: Cogné et al. (2020) "performed a genome-wide association study on 98 Bengal cats to localize an associated region on cat chromosome A3".

Molecular basis: Cogné et al. (2020) "overlaid . . . [the mapping results - see above] with whole-genome sequencing data from a trio of cats from the Bengal research colony . . . . The KIF3B p.Ala334Thr-encoding change was the sole variant that segregated with disease and is predicted to impair the kinesin motor domain".

Clinical features: Ofri et al. (2015): "Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks."

Pathology: Ofri et al. (2015): "Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration."

Genetic testing: The web site of the Veterinary Genetics Laboratory at UC Davis is advertising a DNA test for this disorder: https://www.vgl.ucdavis.edu/services/cat/BengalPRA.php Langford Vets also offer the test: https://www.langfordvets.co.uk/diagnostic-laboratories/services/cat-genetic-testing/ The likely causal variant was published after DNA testing was made available. (Thanks to Maarten de Groot for advising FN of the test (5 May 2017). The likely causal variant was published by Cogné et al. (2020).

Breeds: Bengal (Cat) (VBO_0100040), Highlander (Cat) (VBO_0100114), Highlander Shorthair (Cat) (VBO_0100116), Savannah (Cat) (VBO_0100208).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: