Dominant Blue Eyes (DBE)

Dominant Blue Eyes (DBE)

In cats, blue eye colour can occur as part of several coat colour patterns, such as colourpoint, white spotting, or dominant white. In addition to these well‑known mechanisms, a distinct trait called Dominant Blue Eyes (DBE) has been described in several unrelated cat lines. Cats with DBE may have one or two blue eyes, sometimes accompanied by minimal white markings, although the amount of white and the symmetry of the eye colour can vary widely between individuals.

DBE is genetically heterogeneous, meaning that different genetic variants can produce a similar blue‑eyed phenotype. Several independent variants have been identified in the PAX3 gene, a gene essential for the development and migration of melanocytes. Melanocytes are responsible for pigment production in the coat and eyes, and they also play a critical role in normal inner ear function. As a result, disruptions in melanocyte development can lead to blue eyes and, in some cases, congenital deafness, similar to auditory–pigmentary syndromes described in other species.

DBE follows an autosomal dominant mode of inheritance: a single copy of a DBE‑associated variant is sufficient to produce the trait. However, expression is variable, and some cats carrying a DBE variant may show only subtle pigmentation changes or incomplete expression of blue eye colour. This phenomenon, known as incomplete penetrance, means that the genotype does not always predict the visible phenotype.

To date, all DBE‑affected cats described in scientific studies have been heterozygous for their respective PAX3 variant. The homozygous state has not been documented and may be associated with embryonic lethality or severe pigment‑related defects, depending on the specific variant. Because of this, the phenotype in homozygous cats cannot be reliably predicted.

Given the variability in expression and the presence of multiple distinct PAX3 variants, genetic testing is essential for accurate identification of DBE carriers. Testing supports informed breeding decisions, particularly in cases where the phenotype is subtle or not visibly apparent.

Known variants

Several genetic variants associated with DBE have been identified in cats. Although these variants lead to similar phenotypes, they are genetically distinct and may differ in their expression and associated features.

DBE^ago (PubMed: 40459211)
The DBE^ago variant is located within or near the PAX3 gene, which plays a key role in melanocyte development and migration. This variant disrupts normal gene function and is inherited in an autosomal dominant manner. It is observed in Maine Coon cats and affected animals typically show one or two blue eyes, with variable expression. Some individuals may also exhibit congenital deafness, consistent with the role of melanocytes in inner ear function.

DBE^ALT (PubMed: 38997957)
The DBE^ALT variant affects a genomic region involved in pigmentation pathways and is believed to alter gene expression rather than protein structure. It is observed in multiple breeds and lines (British Longhair, British Shorthair, Exotic Shorthair, Persian, Ragdoll, Sphynx, Exotic Longhair, Altai). Cats carrying this variant display blue eyes with variable expressivity, but there is no consistent association with deafness or other additional traits. Like other DBE variants, it follows autosomal dominant inheritance.

DBE^RE (PubMed: 38869246)
The DBE^RE variant is associated with altered melanocyte development due to a mutation in a pigmentation‑related regulatory region. It is observed in the Maine Coon and inherited in an autosomal dominant manner. Affected cats can have one or two blue eyes with variable expression. Hearing impairment has been reported, though does not appear to be a consistent feature of this variant.

The variants DBE^ago, DBE^ALT and DBE^RE are currently suitable for genetic testing and have been identified in different breeds and breeding lines.

A fourth variant, DBE^Cel variant (PubMed: 38644700) has been described specifically in the Celestial Maine Coon line. In the scientific publication describing this variant, only this particular line is reported, and there is currently no evidence for its presence in the general Maine Coon population. In addition, multiple sequence variations surrounding this mutation have been described, complicating the development of a reliable genetic test. For these reasons, this variant is currently not included in the test panel.

Genetic testing

Genetic testing for Dominant Blue Eyes (DBE) in cats is based on the detection of currently known DBE‑associated variants. However, blue eye colour in cats can also be caused by other genetic mechanisms, such as colourpoint, dominant white, white spotting, or additional pigmentation‑related mutations. Furthermore, not all causative variants for DBE‑like phenotypes have been identified yet.

As a result, a cat with blue eyes may still receive a normal (N/N) result for all known DBE variants. This means that the cat does not carry any of the currently recognised DBE‑associated mutations, but the blue eye colour may be due to another known pathway or a yet‑undiscovered genetic variant.

Relevant tests

• K508 – Dominant Blue Eyes (DBE) – Cat (3 variants)
• K341: Dominant Blue Eyes Agosto (DBE-AGO)
• K506: Dominant Blue Eyes (DBE-RE)
• K507: Dominant Blue Eyes Altai (DBE-ALT)