H. Rah1, D.J. Maggs2; T. Blankenship3; L.A. Lyons1
Naturally occurring inherited retinal degeneration has been recognized in humans, dogs, cats, and rodents. An early-onset retinal degeneration (15 weeks of age) has been noted in Persian cats, but only end-stage of the disease has been described with suggested autosomal recessive condition. Our objective was to further characterize the inheritance, clinical, histologic, and genetic features of this disease.
Twenty-one kittens from 5 litters were bred from mating homozygous affected to heterozygous carriers. Out of total offspring, 52% (11/21) were affected and 43% (9/21) were phenotypically normal carriers. One was lost during study. Thirteen were males with 7 affected (54%) and 8 were females with 4 affected (50%) suggesting no sex bias in disease transmission. Kittens were examined weekly from 2 weeks (eye-opening) to 16 weeks of age. Ophthalmic examination and neuro-ophthalmic examinations were performed to assess vision sight of animals. Extent and speed of pupillary light reflexes were diminished in affected cats by 2-3 weeks of age and decreased further with age. Dazzle reflex was lost in affected animals by 3 weeks. Retinal vascular attenuation was first suspected at 4 weeks. Horizontal pupil diameter was greater in affected cats (7 mm) than in normal phenotype cats (4 mm) at 5 weeks. Altered tapetal reflectivity was first observed at 6 weeks of age and was generalized by 9 weeks. At 15 weeks, marked generalized retinal degeneration was seen in all affected cats. Behavioral testing confirmed total blindness in affected individuals by 16 weeks. Eight enucleated globes from 2 affected and age-matched carriers were assessed histologically. Histological examinations suggest that photoreceptors were present and quickly degenerated between 3-15 weeks. Eleven genes (RPE65, RHO, PDE6B, PDE6A, RDS, RP1, CRX, CRB1, RGPRIP1, GUCY2D and TULP1) that is responsible for inherited blindness in other mammalian species are candidate genes for Persian PRA. Particular regions of six candidate genes (RPE65, RHO, PDE6B, PDE6A, RDS, RP1) with known mutations causing inheritable retinopathies in other species have been examined. Sixteen mutations that are identified mutations in the six genes in other species were scanned for causative mutation in affected Persians. None of these mutations were not found in our Persian cats. One missense mutation was identified in RP1; however, the mutation did not segregate with disease phenotype. Linkage mapping was performed on the pedigree with microsatellite markers to implicate a candidate gene by showing linkage or to exclude a candidate gene by showing negative linkage. Twenty microsatellite markers were evaluated for linkage with the disease phenotype. To date, linkage analyses have been inconclusive.
We have described an autosomal recessive, rod cone dysplasia of Persian cats. Clinical and histologic evidence confirms that disease is present before 3 weeks of age. This evidence may be referred for diagnosis of early onset retinal degeneration in Persian or related breed.