Auditory-pigmentary syndrome, Dominant Blue Eyes, DBE

 

Gene: PAX3

Transmission: Autosomal dominant, variable penetration

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease. Animals with two copies of the mutation generally exhibit more severe symptoms and an earlier onset of the disease than animals with only one copy. One or both parents of an animal carrying the mutation have one or two copies of the mutation. Animals with one or two copies of the mutation can pass the mutation on to their offspring. Alternatively, the disease may result from a de novo mutation.

Mutations:

Allele DBE/CEL (Celetial Dominant Blue Eyes): Insertion (retroviral), PAX3 gene; insertion 395bp retrovirus FERV1, intron4-5, chromosome C1.

Allele DBE/RE (Rociri Elvis Dominant Blue Eyes): Substitution (nonsense), PAX3 gene; c.937C>T, p.(Gln313 STOP), exon6, chromosome C1.

Allele DBE/ALT (Altai Dominant Blue Eyes): Insertion (viral), PAX3 gene; insertion 433bp virus RD-114, intron4-5, chromosome C1.

Allele DBE/AGO (Agostino Dominant Blue Eyes): Deletion, PAX3 gene; c.160 del.C, p.(His54Thr STOP 108), exon2, chromosome C1.

Breeds: Altai, Celestial, British Longhair, British Shorthair, Chinese Tank Cat, Maine Coon, Persian, Ragdoll, Siberian, Sphynx

Medical systems: Dermal, ocular, auditory

Age of onset of symptoms: From birth (congenital).

PAX3-related auditory pigment syndrome is also called “Dominant Blue Eyes” (DBE) and can resemble Waardenburg syndrome in humans and Splashed White phenotype in horses.  Several mutations within the PAX3 gene can result in a deficiency of melanocytes in the skin and hair follicles, resulting in a phenotype of variable white spotting.  A deficiency of melanocytes within the iris can result in unilateral (heterochromia) or bilateral blue eyes.  An absence of melanocytes within the stria vascularis of the inner ear can lead to unilateral or bilateral sensorial deafness with variable penetration.  The DBE/RE allele, as seen originally in a Dutch line of Maine Coon cats, is particularly associated with deafness, and the homozygous state for this mutation may cause embryo lethality.  There is no treatment for sensorial deafness, therefore the DBE/RE mutation should be identified in breeding animals and selection against this mutation should be made.  The DBE/CEL, DBE/ALT and DEB/RE mutations can show variable penetration (called latency), where a cat could be a carrier but does not display the blue eye phenotype. Double heterozygous animals are possible.  It is believed that additional, yet to be characterized mutations can also be associated with blue eyes in cats, warranting further investigation.  Further study on the prevalance of deafness is also needed.

Note that sensorial deafness in the cat can also be caused by mutations in the KIT gene responsible for the Dominant White phenotype:

Deafness (Dominant White, W locus) , OMIA link [0209-9685]

 

References:

OMIA link: [1688-9685]

Abitbol M, Cloquell A, Kaczmarska A, et al. (2025) Dominant blue eyes in Maine Coon cats: New PAX3 variant and updated phenotypic data. Anim Genet 56:e70020. [pm/40459211]

Abitbol M, Couronné A, Dufaure de Citres C, Gache V. (2024) A PAX3 insertion in the Celestial breed and certain feline breeding lines with dominant blue eyes. Anim Genet 55:670-675. [pm/38644700]

Abitbol M, Dufaure de Citres C, Rudd Garces G, et al. (2024) Different founding effects underlie dominant blue eyes (DBE) in the domestic cat. Animals (Basel) 14:1845.  [pm/38997957]

Rudd Garces G, Farke D, Schmidt MJ, et al. (2024) PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome. G3 (Bethesda) 14:jkae131. [pm/38869246]

 

Contributed by: Cassie Champoux and Anya Cloutier-Vilhuber, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)