Auditory-pigmentary syndrome, PAX3-related

 

Gene: PAX3

Transmission: Autosomal, dominant

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.  Alternatively, the disease is caused by 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.

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

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.  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.  It is believed that additional, yet to be characterized mutations can also be associated with blue eyes in cats, warranting further investigation.

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, 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)