DBE Rociri Elvis (DBE-RE)

Overview

DBE-RE is a coding nonsense variant of the PAX3 gene, first described by Rudd Garces et al. (2024) in Maine Coon cats.³

Unlike DBE-CEL and DBE-ALT, which are intronic variants with proposed regulatory effects, DBE-RE occurs within the protein-coding sequence of PAX3. The variant introduces a premature stop codon and is predicted to disrupt normal PAX3 function.

Location

DBE-RE is located in exon 6 of the PAX3 gene on chromosome C1.³

How Does It Work?

DBE-RE is a coding nonsense variant, PAX3:c.937C>T, with the predicted protein-level consequence PAX3:p.(Gln313*).

The nucleotide substitution changes the codon for glutamine at amino-acid position 313 into a premature stop codon. The variant is therefore predicted to result in PAX3 haploinsufficiency.

This differs from DBE-CEL and DBE-ALT, which are intronic insertions located near regulatory elements and do not alter the PAX3 protein-coding sequence.

Associated Phenotype

Cats carrying the DBE-RE variant have been reported with:

  • two blue eyes;

  • heterochromia iridis, commonly described as odd eyes;

  • minimal white spotting;

  • sensorineural hearing loss.

Latent, non-expressing DBE-RE cats carrying the variant without displaying the blue-eye phenotype have also been reported.⁴

The phenotype partially resembles human Waardenburg syndrome, which is associated with reduced PAX3 function and includes abnormalities of pigmentation and sensorineural hearing loss.³

Hearing

DBE-RE has been associated with hearing impairment in heterozygous cats.

In the original study, all eight heterozygous DBE-RE cats examined using BAER testing had unilateral or bilateral hearing loss. A subsequent 2025 study BAER-tested six additional heterozygous DBE-RE cats, all of which had normal bilateral hearing.

The available evidence therefore supports an association between DBE-RE and an increased risk of hearing impairment, but deafness is not fully penetrant. Its prevalence cannot yet be determined from the limited number of BAER-tested animals.

Current State of Knowledge

Current knowledge of DBE-RE is based on two peer-reviewed studies involving cats from the same Maine Coon lineage.

The original study investigated eight stillborn kittens from the pedigree. Six were heterozygous for DBE-RE and two were homozygous for the wild-type allele. None was homozygous for DBE-RE, and the authors concluded that the deaths were not correlated with the PAX3 genotype.³

The subsequent 2025 study identified latent, non-expressing DBE-RE cats and heterozygous DBE-RE cats with normal bilateral hearing. These findings demonstrate variable expression of both the eye-pigmentation and hearing phenotypes within the lineage.⁴

To date, no genetically confirmed homozygous DBE-RE cat has been described in the scientific literature. Consequently, the biological effects of inheriting two copies of the DBE-RE variant remain unknown.

References

  1. Rudd Garces G, Farke D, Schmidt MJ, Letko A, Schirl K, Abitbol M, Leeb T, Lyons LA, Lühken G. PAX3 haploinsufficiency in Maine Coon cats with dominant blue eyes and hearing loss resembling the human Waardenburg syndrome. G3: Genes|Genomes|Genetics. 2024;14(9):jkae131. doi:10.1093/g3journal/jkae131.

  2. Abitbol M, Cloquell A, Kaczmarska A, Holmes K, Lühken G, Macaulay K. Dominant blue eyes in Maine Coon cats: New PAX3 variant and updated phenotypic data. Animal Genetics. 2025;56(3):e70020. doi:10.1111/age.70020.