Description: XL-PRA belongs to the group of progressive retinal atrophies. XL means the mutation is linked to the X chromosome (female chromosome). Initially, the retina develops normally in affected individuals. The first clinical signs are observed within ERG examination 6 months of age. Later, irregular damage to rods light-receptors is observed. Damage to the suppositories occurs only in the final stages of the disease. Affected individuals are usually completely blind by the age of 4 (Zeiss et al. 2002). The causal mutation XL-PRA1 is found in the RPGR gene encoding retinitis pigmentosa GTPase regulator. The mutation causes a premature stop codon. The resulting mutated protein is only able to perform its function to a limited extent. Loss of function is not critical at the beginning of light-sensitive cell development, but light-sensitive cells are not viable in the long term (Zeiss et al. 2002).
The only reliable prevention of XL-PRA1 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: delGAGAA in RPGR gene
Sample: EDTA whole blood (1.0 ml) or 2 buccal brushes
The analysis is suitable for the following breeds: Siberian husky, Samoyed
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.