DBE Agostino (DBE-AGO)
Overview
DBE-AGO is the fourth currently characterised PAX3 variant associated with the Dominant Blue Eyes phenotype. It was first described by Abitbol et al. (2025) in the Agostino Maine Coon lineage.
Unlike DBE-CEL and DBE-ALT, which are intronic variants with proposed regulatory effects, DBE-AGO is a coding frameshift variant predicted to produce a severely truncated PAX3 protein.
Location
DBE-AGO is located in exon 2 of the PAX3 gene on chromosome C1.
How Does It Work?
DBE-AGO is caused by a single-base deletion, PAX3:c.160del.
The deletion shifts the reading frame and introduces a premature stop codon. It is predicted to produce a truncated PAX3 protein, PAX3:p.(His54ThrTer108), lacking approximately 78% of the amino acids present in the wild-type protein.
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
In the original publication, DBE-AGO was associated with:
two blue eyes;
heterochromia iridis, commonly described as odd eyes;
minimal white spotting.
Some cats also showed more extensive white spotting caused by a separate white-spotting allele of the KIT gene.
All 13 genetically characterised DBE-AGO cats in the study were heterozygous for the variant.
Hearing
No deafness was reported by breeders in the Agostino lineage.
However, none of the genetically characterised DBE-AGO cats underwent formal BAER testing. It is therefore not currently possible to determine whether DBE-AGO is associated with unilateral or bilateral hearing impairment.
The absence of breeder-reported deafness should not be interpreted as equivalent to a normal BAER result.
Current State of Knowledge
DBE-AGO is currently described in a single peer-reviewed study.
All 13 genetically characterised DBE cats from the Agostino lineage were heterozygous for PAX3:c.160del. The variant was absent from the non-DBE relatives examined and from all control cat genomes (n > 300).
No latent, non-expressing DBE-AGO cat was identified in the studied family, although the number of animals examined remains limited.
No genetically confirmed homozygous DBE-AGO cat has been described in the scientific literature. Its association with hearing impairment, full phenotypic spectrum and biological consequences in homozygous cats therefore remain unknown.
References
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.