Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice-site variant in Hermansky-Pudlak Syndrome 5 gene

Pigment Cell Melanoma Res. 2020 Nov;33(6):814-825. doi: 10.1111/pcmr.12906. Epub 2020 Jun 29.


In the feline Donskoy breed, a phenotype that breeders call "pink-eye," with associated light-brown skin, yellow irises and red-eye effect, has been described. Genealogical data indicated an autosomal recessive inheritance pattern. A single candidate region was identified by genome-wide association study and SNP-based homozygosity mapping. Within that region, we further identified HPS5 (HPS5 Biogenesis Of Lysosomal Organelles Complex 2 Subunit 2) as a strong candidate gene, since HPS5 variants have been identified in humans and animals with Hermansky-Pudlak syndrome 5 or oculocutaneous albinism. A homozygous c.2571-1G>A acceptor splice-site variant located in intron 16 of HPS5 was identified in pink-eye cats. Segregation of the variant was 100% consistent with the inheritance pattern. Genotyping of 170 cats from 19 breeds failed to identify a single carrier in non-Donskoy cats. The c.2571-1G>A variant leads to HPS5 exon-16 splicing that is predicted to produce a 52 amino acids in-frame deletion in the protein. These results support an association of the pink-eye phenotype with the c.2571-1G>A variant. The pink-eye Donskoy cat extends the panel of reported HPS5 variants and offers an opportunity for in-depth exploration of the phenotypic consequences of a new HPS5 variant.

Keywords: BLOC2S2; Felis catus; Hermansky-Pudlak Syndrome 5; albinism; ruby-eye 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism, Oculocutaneous / genetics*
  • Alleles
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Cats
  • Chromosomes, Mammalian / genetics
  • Disease Models, Animal
  • Exons / genetics
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Homozygote
  • Humans
  • Mice
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • RNA Splice Sites / genetics*
  • RNA Splicing / genetics


  • Carrier Proteins
  • RNA Splice Sites