DBE Celestial (DBE-CEL)

Overview

DBE-CEL is a non-coding intronic variant of the PAX3 gene, first described by Abitbol et al. (2024). It consists of a FERV1 LTR insertion within intron 4 of PAX3, close to conserved non-coding elements involved in the regulation of PAX3 expression. It is currently the best-characterised non-coding variant associated with the Dominant Blue Eye (DBE) phenotype.

Location

The DBE-CEL variant is located within intron 4 of the PAX3 gene on chromosome C1. Because introns are non-coding regions, the mutation does not become part of the final protein sequence.

Molecular Mechanism

DBE-CEL is a non-coding intronic variant with a proposed regulatory effect.

Because the insertion lies outside the protein-coding sequence, it is not predicted to alter the amino acid sequence of the PAX3 protein directly. Its position close to regulatory elements in intron 4 instead suggests it may influence PAX3 expression during development. This effect is inferred from the variant's location and has not yet been directly measured in DBE-CEL cats.

This distinguishes DBE-CEL from coding variants such as DBE-RE and DBE-AGO, which alter the protein-coding sequence and are predicted to produce abnormal or truncated PAX3 proteins.

Associated Phenotype

Published cases have associated DBE-CEL with a range of eye pigmentation patterns, including:

  • bilateral blue eyes

  • odd eyes

  • sectoral heterochromia

  • latent (non-expressing) cats

The degree of expression appears to be variable, suggesting that additional genetic or developmental factors may influence the final phenotype.

Hearing

BAER testing of DBE-CEL heterozygous cats has not shown evidence of an association between the variant and deafness (Abitbol, Couronné, et al., 2024).

Among 47 BAER-tested DBE-Celestial cats, three were diagnosed with unilateral deafness and none with bilateral deafness. The three unilaterally deaf cats had concurrent ear conditions unrelated to DBE and the authors concluded that the DBE-CEL variant did not appear to be associated with deafness in heterozygous cats.

At present, this distinguishes DBE-CEL from some coding PAX3 variants, which have been associated with hearing impairment.

Current Evidence

One genetically confirmed DBE-CEL/DBE-CEL kitten has been reported in the scientific literature. The kitten was genetically confirmed as homozygous for the DBE-CEL insertion; it was white, had a cleft palate and died at birth, and limb abnormalities were also reported by the breeder. What is established for this individual is its genotype, not the cause of these findings: no study has demonstrated that DBE-CEL homozygosity causes them. A single case cannot establish causation, and it remains unknown whether any, some or all of these abnormalities were related to the genotype, to other genetic or developmental factors, or to unrelated causes.

No genetically confirmed living homozygous DBE-CEL cat has been described in the scientific literature to date.

This absence of published cases should not be interpreted as evidence that living DBE-CEL homozygotes do not exist. It indicates only that no such cat has yet been genetically documented and described in the peer-reviewed literature.

Unpublished breeder reports cannot establish the phenotype or viability of DBE-CEL homozygotes unless the cats are individually genotyped and their clinical findings are documented.

References

Abitbol M. et al. (2024). A PAX3 insertion in the Celestial breed and certain feline breeding lines with dominant blue eyes.Animal Genetics, 55(4), 670–675.