Description: XL-PRA belongs to the group of progressive retinal atrophies. XL means the mutation is linked to the X chromosome (female chromosome). Microdeletions resulting in a premature stop (XL-PRA1) or a frameshift mutation (XL-PRA2) result in very different retinal phenotypes, which are allele-specific and consistent for each mutation. The phenotype associated with the frameshift mutation in XLPRA2 is very severe and manifests during retinal development. The causal mutation XL-PRA2 is found in the RPGR gene encoding retinitis pigmentosa GTPase regulator. XLPRA2 carriers often show progressive disease that results in advanced retinal degeneration by 5–6 years of age. In heterozygotes, the retinal functional abnormalities reflected the underlying photoreceptor pathology. The retina of XLPRA2 carrier failed to develop normally, and surviving photoreceptors showed severely structural abnormalities.

 

The only reliable prevention of XL-PRA2 disease is to exclude female carriers from breeding!

 

Two types of XL-PRA have been identified:

1) XL-PRA1 in the breed Siberian Husky and Samoyed

2) XL-PRA2 in the breed Miniature Schnauzer

 

Inheritance: X-linked, Males are never carriers of X-linked disease!

 

Mutation: del1084–1085 in RPGR gene

 

Sample: EDTA whole blood (1.0 ml) or 2 buccal brushes

 

The analysis is suitable for the following breeds: Miniature Schnauzer

 

Notes: Inheritance of X-linked disease:

Females have genotype XX. So three variants are possible in females as regards XL-PRA disease:

XnXn – females with two normal X chromosomes = normal phenotype, a healthy female

XnXm – females with one normal X (Xn) and one mutant X (Xm) = a female carrier. The clinical disability of female carriers is individual, depending on the X chromosome inactivation. It means that a gene expression on the X chromosome is different in different cells. Usually, female carriers are without any disability. Nevertheless, the degree of disability can be from mild to very serious.

XmXm – females with two mutated X chromosomes = an affected female

 

Males have XY chromosomes. So they have two possibilities as regards XL-PRA disease:

XnY – normal phenotype, a healthy male

XmY – an affected male; he inherited mutated X chromosome from his mother

 

Example of mating a healthy male with a female carrier:

As can be seen from the picture, by mating a female carrier and a healthy male, half of the females will be healthy, half will transmit XL-PRA to the offspring, half of the males will be healthy and half will be affected.