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X Linked Progressive Retinal Atrophy 2 (XLPRA2)
| Acronym: | XLPRA2 |
| Gene: | RPGR |
| Mutation: | c.3472_3473del |
| Inheritance: | X linked recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
X-linked progressive retinal atrophy 2 (XLPRA2) is an eye disorder, which belongs to the progressive retinal atrophy group of disorders. Progressive retinal atrophy (PRA) comprises autosomal recessively inherited diseases that lead to degeneration of retinal photoreceptor cells in dogs and other pets. In general, these diseases are characterized by disturbance of night vision, visual field defects, and abnormalities in the electroretinogram, which can progress to blindness. 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. PRA appears in most dog breeds, but also in mixed breed dogs. Almost all PRA disorders are recessively inherited, with exceptions of dominant and X-linked PRA inheritance (XLPRA) in a few breeds, such as Old English Mastiffs, Bullmastiffs, Siberian Husky, and Samoyed.
Rods are important for vision in dim light, or also night vision and PRA with its rode degeneration leads to night blindness. In the research, it is estimated that PRA causes the death of around 95% of the dog’s photoreceptors. For dog owners or breeders, PRA is recognized by a ”glow” or ”increased shine” in the eyes. The disease can progress, from the initial stage of night blindness to the advanced stage of PRA which causes secondary cataracts or full blindness in the dog. The advanced stage of PRA usually occurs within one year after the appearance of the first symptoms. After the death of rods, oxygen is still being delivered to the dead rods, which they cannot use. This excessive oxygen is toxic to surrounding cells - it causes oxidative damage and consequently, cone death. The death of retinal tissue causes the release of toxic products of cells. They are absorbed by the lens, which causes lens damage and cataract development.
The disorder is caused by a deletion in the RPGR gene. XLPRA is inherited as an X-linked recessive disorder, and as such, it differently affects males and females. A heterozygous female with one copy of the mutated gene will not develop symptoms of the XLPRA and she is the carrier of the disorder. When mated with a healthy male, all female puppies will be healthy, but there are 50% chances they will be carriers of the disease. Among male puppies, chances are 50% that they will be healthy, and 50% that they will be affected and with time show the XLPRA2 symptoms. There is no cure for XLPRA2 and the only way to prevent it is to breed dogs that are not carriers of the mutation. Defected genes for autosomal recessive disease can be passed for many generations without affected individuals occurring until two carriers are bred to one another. The only way to find out if there is a chance of getting an affected puppy is to do XLPRA2 genetic testing.
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 (female) or hemizygous state (male) (i.e. only healthy allele on X chromosome). 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 mutated allele in homozygous state (female) or hemizygous state (male) (i.e. only mutated allele on X chromosome). 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.
** Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Zeiss, C., J., (2000.): Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3). Hum. Mol. Genetic. 9(4): 531-537.
Beltran, WA., (2009): Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGR exon ORF15 mutations. Invest Ophthalmol Vis Sci. 50(8): 3985-95.
Zhang, Q., Acland, G.M., Wu, W.X., Johnson, J.L., Pearce-Kelling, S., Tulloch, B., Vervoort, R., Wright, A.F., and Aguirre, G.D. (2002). Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration. Hum. Mol. Genet. 11, 993–1003.