DBE Altai (DBE-ALT)

Overview

DBE-ALT is a non-coding intronic variant of the PAX3 gene, first described by Abitbol et al. (2024). It consists of an RD-114 LTR insertion within intron 4 of PAX3, close to conserved non-coding elements involved in the regulation of PAX3 expression, and represents an independently arising Dominant Blue Eye (DBE) variant.

Although DBE-ALT is located within the same intron as DBE-CEL, it originated from a different endogenous retroviral insertion and should therefore be considered a distinct genetic variant rather than a subtype of DBE-CEL.

Location

The DBE-ALT variant is located within intron 4 of the PAX3 gene on chromosome C1.

Molecular Mechanism

DBE-ALT 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. Like DBE-CEL, 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-ALT cats.

Although both variants affect intron 4, they arose independently through different retroviral insertion events and should be regarded as separate molecular variants.

Associated Phenotype

Published cases have associated DBE-ALT with a range of eye pigmentation phenotypes, including:

  • bilateral blue eyes

  • odd eyes

  • sectoral heterochromia

  • latent (non-expressing) cats

As with other DBE variants, expression appears to be variable, and additional genetic or developmental modifiers are likely to influence the final phenotype.

Hearing

Based on the currently available published data, hearing loss has not been reported in heterozygous DBE-ALT cats.

Deafness has been associated with compound heterozygosity and homozygosity.

Relatively few genetically characterised animals have been described for these combined genotypes, and further studies are needed to better define the clinical spectrum of this variant.

Current State of Knowledge

DBE-ALT was first identified in 2024 as one of the independently arising PAX3 variants associated with the Dominant Blue Eye phenotype.

Unlike DBE-CEL, surviving homozygous (RD/RD) DBE-ALT cats have been reported. Three were described, all white or almost white: one (Nanotigr line) was reported deaf by its owner, while two (Altai line) were considered to hear normally by their breeder. As BAER testing was not performed on these two, unilateral deafness could not be excluded. Their existence confirms that homozygous DBE-ALT cats are viable, but the number of genetically confirmed homozygotes remains very small, and BAER-tested cases are needed to define the clinical spectrum accurately.

Current knowledge of DBE-ALT remains considerably more limited than that of DBE-CEL, and further research is needed to fully characterise this variant.

References

Abitbol M. et al. (2024). Different Founding Effects Underlie Dominant Blue Eyes (DBE) in the Domestic Cat Animals, 14(13), 1845.