Cystinuria type 3 is an inherited disease affecting kidney function in dogs. Dogs with cystinuria are deficient of a specific protein the kidneys use to transport cystine. Normal kidneys reabsorb cystine so that only small amounts pass into the urine. Dogs with cystinuria fail to reabsorb cystine, allowing large amounts to pass into the urine. Excessive cystine can form crystals and/or stones in the urinary tract, which can block the ureters or Urethra and stop the normal flow of urine. Symptoms of disease include straining to urinate, blood in the urine, frequent urination of small volumes or inability to urinate. Dogs with cystinuria often have recurrent inflammation of the urinary tract and if not treated, urinary stones can cause urinary tract infections, kidney failure and even death. Affected males are also at increased risk for urinary obstruction due to anatomical differences.
This test examines the genome for a genetic Mutation in the SLC3A1 gene associated with cystinuria type 3 (Variant 2). This mutation is not the actual mutation responsible for the disorder. It is considered a “linked marker” for cystinuria type 3. Linked markers are present in close proximity to the disease-causing mutation and are predictably inherited along with it. Making a test for the genetic mutation in the SLC3A1 gene a useful tool to assess cystinuria risk. Dogs that inherit one copy of the SLC3A1 mutation are considered carriers of the disease and will not show clinical signs of cystinuria. Cystinuria type 3 is an androgen-dependent form of the disease. Therefore, only intact males (and not females) are at an increased risk. Male dogs which inherit two copies of the SLC3A1 mutation are considered affected with cystinuria type 3 and may develop clinical signs. Although, female dogs with the SLC3A1 mutations should not develop clinical signs, they can produce at-risk/affected male offspring if bred with a dog that has also inherited these mutations.
This test also examines the genome for a genetic mutation in the SLC7A9 gene speculatively associated with cystinuria type 3 (Variant 3). This mutation is not believed to be the actual mutation responsible for the disorder. However, it may be a “linked marker” for cystinuria type 3, meaning that this marker may be present in close proximity in the genome to the mutation responsible for cystinuria type 3 and may be inherited along with the mutation which causes this disease. However, it is unconfirmed at this time if one or two copies of the SLC7A9 mutation alone is associated with cystinuria type 3.
Breed-Specific Information for the French Bulldog
The Mutation of the SLC3A1 gene associated with cystinuria type 3 (Variant 2) has been identified in the French Bulldog, although its overall frequency in this breed is unknown. The mutation of the SLC7A9 gene associated with cystinuria type 3 (Variant 3) has been identified in the French Bulldog, although its overall frequency in this breed is unknown.
Genetic testing of the SLC3A1 gene will reliably determine whether a dog is a genetic Carrier of cystinuria type 3. Cystinuria type 3 is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of either of the linked markers (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the SLC3A1 markers, there is a risk of having affected male pups. Each pup that is born to this pairing has a 50% chance of inheriting one copy and a 25% chance of inheriting two copies of the Mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood, genetic testing should be performed before breeding. To eliminate the mutation from breeding lines and avoid the potential of producing affected pups, breeding dogs known to carry the same markers to each other is not recommended.
Genetic testing of the SLC7A9 gene will reliably determine whether a dog is a genetic carrier of a mutation speculatively associated with cystinuria type 3. Cystinuria type 3 is inherited in an autosomal recessive manner in dogs meaning that they must receive two copies of the linked marker in SLC3A1 (Variant 2) (one from each parent) to develop the disease. It is also speculated that dogs which inherit one or two copies of the SLC7A9 mutation in the absence of the SLC3A1 mutation may also be affected with cystinuria type 3. However, this has not yet been confirmed in the peer-reviewed scientific literature. Owners of dogs which have inherited one or two copies of the SLC7A9 mutation should consult with their veterinarian about assessing the dog’s urinary cystine levels to confirm the presence of excessive cystine excretion. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood, genetic testing should be performed before breeding. To eliminate this mutation from breeding lines and avoid the potential of producing affected pups, breeding dogs known to carry the same SLC3A1 (variant 2) marker is not recommended. In addition, until further evidence of the significance of the SLC7A9 (Variant 3) mutation is obtained, breeding of dogs that that are carriers of this mutation should be done with caution and under consultation with your veterinarian. Dogs that are not carriers of the linked markers in either SLC3A1 or SLC7A9 have no increased risk of having affected pups.
There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.
Harnevik L, Hoppe A, Soderkvist P. SLC7A9 cDNA cloning and mutational analysis of SLC3A1 and SLC7A9 in canine cystinuria. Mamm Genome. 2006 Jul;17(7):769-76.