Retinal atrophy, cone degeneration (Achromatopsia 3)

Gene: CNGB3

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Alaskan Malamute, Australian Shepherd mutation: Deletion, CNGB3 gene; complete deletion of CNGB3 gene

German Shorthaired Pointer mutation: Substitution, CNGB3 gene; c.784 G>A, p.(D262N), exon6

Medical system: Ocular

Breeds: Alaskan Malamute, Alaskan Sled Dog, American Staffordshire Terrier/Amstaff, Australian Shepherd, German Shorthaired Pointer, Labrador Retriever, Miniature Australian Shepherd, Siberian Husky

Age of onset of symptoms: Between 8 to 12 weeks

Progressive retinal atrophy (PRA) refers to a group of diseases affecting the retina.  PRA-Cone Degeneration is a disease that affects cone receptor cells, responsible for color vision.  This results in reduced acuity of day vision and loss of color vision.  Puppies begin to lose their daytime vision around 8 to 12 weeks of age and start to show signs of sensitivity to light.  Rod receptor cells, responsible for peripheral vision and vision in low light, are normal in affected dogs such that they do not lose their night vision.

References:

OMIA link: [1365-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Genetics Committee of the American College of Veterinary Ophthalmologists. (2021) The Blue Book: Ocular disorders presumed to be inherited in purebred dogs. 13th Edition.  [https://ofa.org/wp-content/uploads/2022/10/ACVO-Blue-Book-2021.pdf]

Dixon CJ. (2016) Achromatopsia in three sibling Labrador Retrievers in the UK. Vet Ophthalmol 19:68-72. [pubmed/25752464]

Palanova A. (2016) The genetics of inherited retinal disorders in dogs: implications for diagnosis and management.  Vet Med (Auckl). 7:41-51. [pubmed/30050836]

Yeh CY, Goldstein O, Kukekova AV, et al. (2013) Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia. BMC Genet 14:27. [pubmed/23601474]

Sidjanin DJ, Lowe JK, McElwee JL, et al. (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achronatopsia locus ACHM3.  Human Molecular Genetics 11(6):1823-1833. [pubmed/12140185]