Retinal atrophy, progressive, Type III (FAM161A related)

Gene: FAM161A

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.

Mutation: Insertion, FAM161A gene; c.1758 ins.238pb (SINE), exon5

Medical system: Ocular

Breeds: Tibetan Spaniel, Tibetan Terrier

Age of onset of clinical signs: around 5 years of age

Progressive retinal atrophy type III is a degenerative disease affecting the photoreceptor cells of the retina. Symptoms appear around the age of 5 and include various bilateral and symmetrical changes in the retina, such as increased reflectivity of the tapetum lucidum, vascular attenuation, pigmentation changes and including atrophy of the optic nerve. Rod photoreceptors, responsible for low-light and peripheral vision, are destroyed first, resulting in night blindness. Eventually the cone photoreceptors, responsible for daylight and color vision, are affected, leading to total vision loss.

References:

OMIA link: [1918-9615]

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]

Bunel M, Chaudieu G, Hamel C, Lagoutte L, et al. (2019) Natural Models for Retinitis Pigmentosa: Progressive Retinal Atrophy in Dog Breeds.  Hum Genet. 138(5):441-453. [pubmed/30904946]

Downs LM, Aguirre GD. (2016) FAM161A and TTC8 Are Differentially Expressed in Non-Allelelic Early Onset Retinal Degeneration. Adv Exp Med Biol. 854:201-7. [pubmed/26427412]

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

Downs LM, Mellersh CS. (2014) An intronic SINE insertion in FAM161A that causes exon-skipping is associated with progressive retinal atrophy in Tibetan Spaniels and Tibetan Terriers.  PLOS ONE 9(4):e93990. [pubmed/24705771]