The currently characterised DBE variants all lie within a single gene, PAX3, on feline chromosome C1.¹ ² ³ ⁴ Other, as-yet-unresolved DBE lineages may have a different molecular basis, but this has not been established.

DBE does not exist in isolation. PAX3 encodes a transcription factor that plays an important role in neural-crest development, including the formation, migration and differentiation of melanocytes. Because melanocytes also contribute to normal inner-ear function, disruption of this developmental pathway can affect pigmentation and, in some genotypes, hearing. Variants affecting this pathway produce comparable pigmentary — and sometimes auditory — phenotypes across many species, including mice, dogs, horses and humans.³ In mice, variants in the PAX3 homologue produce the classic Splotch phenotype, and in humans, PAX3 variants cause Waardenburg syndrome types 1 and 3.³

Waardenburg syndrome is named after the Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg, who first described it in 1951. In humans, PAX3-associated Waardenburg syndrome is defined by features that can include pigmentary changes of the iris, skin and hair, and congenital sensorineural hearing loss.³

This illustrates an important point of perspective. Many of the same genes that produce recognised coat colours or eye colours in domestic animals are described, in humans, as "syndromes" or "genetic disorders." The underlying biology is shared; the framing differs. For example:

• ASIP — in mice, variants produce the yellow, obese agouti phenotype; in cats, ASIP governs normal tabby (agouti) banding of the coat.

• TYR — in humans, TYR variants cause oculocutaneous albinism with increased skin-cancer risk; in cats, the same gene produces the colourpoint and albino series.

• KIT —different variants in this gene can produce very different biological effects. In humans, certain germline KIT variants cause piebaldism, while distinct activating KIT mutations are involved in some cancers, including gastrointestinal stromal tumours. In cats, KIT variants are responsible for dominant white and white spotting.

Viewed in this wider biological context, feline DBE is one example of how variation in a conserved developmental gene can influence pigmentation across mammals. The underlying biological pathways may be shared between species, while the resulting phenotype and health consequences depend on the specific gene, variant and genotype involved.

Note: the founder histories below (names, dates, cattery origins) come from breeder and community records. The genetic findings are drawn from the peer-reviewed literature and are cited accordingly.

DBE-ALT (Altai)

According to breeder records, blue-eyed cats were noticed among street cats in Ust-Kamenogorsk, Kazakhstan, in the mid-to-late 1990s, and were used to develop the Altai line. Community sources name early founders including a semi-longhaired cat with odd eyes (one blue, one yellow-green) and a black cat, Fyodor, with a blue eye and a white tail-tip — a phenotype compared at the time to the American Ojos Azules. The dominant blue-eye trait in these cats was inherited dominantly but not always visibly expressed.

The trait was later characterised genetically. DBE-ALT is an RD-114 LTR insertion in intron 4 of PAX3, associated with DBE in Altai cats and several other lineages, and consistent with autosomal dominant inheritance and incomplete penetrance.²

To date, three homozygous (RD/RD) DBE-ALT cats have been reported: two in the Altai line, described by their breeder as hearing (though no BAER testing was performed, so unilateral deafness could not be excluded), and one in the Nanotigr line, reported deaf by its owner. All three were white or almost white.²

A prominent white tail-tip — sometimes extending over part of the tail — is often described by breeders as characteristic of Altai-line cats. This is a breeder observation rather than a documented diagnostic feature.

DBE-CEL (Celestial)

The variant now designated DBE-CEL was previously grouped by breeders together with the Altai gene. It was characterised in 2024 by Prof. Marie Abitbol and colleagues and shown to be a distinct variant, separate from DBE-ALT.¹ ²

DBE-CEL is a FERV1 LTR insertion in intron 4 of PAX3, showing autosomal dominant inheritance with variable expression and incomplete penetrance.¹

In heterozygous cats studied to date, DBE-CEL has not been associated with deafness, and affected cats did not show dystopia canthorum — a facial feature seen in PAX3-associated forms of human Waardenburg syndrome.¹ ²