Blue eyes in Felis catus: genetics and health impacts

Blue eyes and a colored coat are a sought-after trait in Felis catus. The dominant blue eye (DBE) phenotype arises from mutations within the PAX3 gene and is characterized by blue eyes on the background of a colored coat. Our review of the literature highlights the characteristics of four DBE variants, DBECEL, DBERE, DBEALT and DBEAGO, emphasizing their diverse phenotypic expressions, including blue eye color and white spotting to associated risks of sensorineural hearing loss (SNHL) across cat breeds. We also highlight breed-specific disorders arising from limited gene pools, and given pathological effects of inbreeding and posit that responsible breeding strategies must prioritize genetic diversity to improve animal welfare. As DBERE variants resulted in high kitten mortality, with homozygous variants predicted to result in prenatal lethality and heterozygosity associated with a risk of SNHL and continuing to breed with this gene cannot be considered ethical under German Law. DBEALT, DBECEL and DBEAGO heterozygote felines have not yet been shown to exhibit SNHL. We sought to categorize DBE variant effects on cats, understand if this is comparable to other species and explain further the mechanism between eye color and SNHL. Blue eyes in cats may arise through several different genetic mechanisms. Whilst blue eyes are commonly associated with white coats or colorpoint patterns, this can also occur with a fully colored coat. This is a trait referred to as “dominant blue eyes” (DBE). Several DBE variants affecting the paired box 3 (PAX3) gene have now been identified. Some of these variants may also be associated with hearing loss or other health concerns. This review summarizes current knowledge of the genetics of blue eyes in cats, compares DBE variants, and discusses why genetic testing, hearing assessment, and responsible breeding decisions are important when it comes to cats with blue eyes.