Deutsch
Hrvatski
Русский
Português
Sheltie Progressive Retinal Atrophy (CNGA1-PRA)
| Acronym: | CNGA1-PRA |
| Gene: | CNGA1 |
| Mutation: | c.1752_1755delAACT |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Sheltie Progressive Retinal Atrophy is an inherited disorder that belongs to a group of eye disorders known as progressive retinal atrophy. Progressive retinal atrophy (PRA) includes autosomal recessively inherited diseases that lead to degeneration of retinal photoreceptor cells in dogs and other pets. It is a canine equivalent to retinitis pigmentosa (RP), an inherited eye disorder affecting human beings. The first case of PRA was observed in England more than a hundred years ago. In general, PRA is characterized by disturbance of vision in the dark, visual field defects, and abnormalities in the electroretinogram. It appears in both eyes simultaneously. The age of onset and rate of retinal degeneration varies between the different forms of the conditions. Some forms of PRA are common to multiple dog breeds, while others are recognized in just a single breed. Until now, it has been identified in more than 100 dog breeds. Almost all forms of PRA are inherited in a recessive manner, with exceptions in some breeds such as Old English Mastiffs, Bullmastiffs, Siberian Husky, and Samoyed where forms of PRA are inherited as dominant or X-linked disorders.
There are two types of photoreceptors in the eye, rods, and cones. Rods have an important role in vision in dim light and also night vision. PRA causes rode degeneration and in this way leads to night blindness. Researchers estimated that PRA causes the death of around 95% of the dog’s photoreceptors. Dog owners or breeders recognize PRA by ”glow” or ”increased shine” in the eyes. The disease is progressive. The initial stage is characterized by night blindness, while the advanced stage of PRA can cause full blindness in the dog. After the appearance of the first symptoms, it usually takes one year for the disorder to progress from the initial to the advanced stage, causing severe and irreversible damage to the dog’s eye. Sheltie Progressive Retinal Atrophy (CNGA1-PRA) is a form of PRA with adult onset, with an average of developing first symptoms at 5 years of age.
Sheltie Progressive Retinal Atrophy (CNGA1-PRA) is an inherited autosomal recessive disease. It is caused by a mutation in the CNGA1 (cyclic nucleotide gated channel alpha 1) gene. This gene encodes for a protein expressed in the outer segment of rod photoreceptors in the retina. The mutation is a 4-base pair deletion, which results in a premature stop codon and expression of truncated protein. A dog can be clear, carrier, or affected. Carriers of the gene are heterozygous and do not develop the disease’s symptoms. When mating two carrier dogs, each future cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Wiik et al., Progressive retinal atrophy in Shetland Sheepdog is associated with a mutation in CNGA1 gene. Amin Genet. 2015 Oct, 46(5):515-21.
Karlstam et al., A slowly progressive retinopathy in the Shetland Sheepdog. Vet Ophthalmol. 2011 Jul; 14(4):227-38. retinal degeneration called Slow Progressing Retinopathy ( SPR ) that progresses more slowly and does not cause such obvious visual impairment as does PRA.