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Canine Cystinuria Newfoundland Type (CYS)
| Acronym: | CYS, CYS-IA |
| Gene: | SLC3A1 |
| Mutation: | c.586C>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Cystinuria is an inherited renal disorder in which increased amounts of amino acids cystine, lysine, arginine, and ornithine are excreted in the urine. It has been detected in humans, dogs, cats, and other animals. Canine cystinuria has been identified for the first time in 1823 as the first reported metabolic disorder in dogs. So far it has been reported in more than 70 dog breeds, most frequently in Dachshund, Basset Hound, Irish Terrier, and English Bulldog. Its higher occurrence has been recorded in European countries such as Germany and Sweden. In human patients, as well as in affected dogs, cystinuria appears to be a very heterogeneous disorder. In humans, it can be divided into three groups, type I caused by mutations in the SLC3A1 gene, and types II and III, caused by mutations in the SLC7A9 gene. Cystinuria affecting the Newfoundland dog breed shares similarities with human cystinuria type I.
In properly functioning kidneys, blood is filtered in order to create urine. Cystine is reabsorbed back into the bloodstream within the tubules. Dog affected with cystinuria cannot reabsorb cystine back in their bloodstream, which causes cystine accumulation in the urine. In case that urine becomes more concentrated in the kidneys, redundant cystine forms crystals because cystine is insoluble in acidic pH urine. Some crystals can combine with calcium molecules, grow, and get stuck in the kidneys or in the bladder, creating blockages in the urinary tract. These stones can also be a source of bacterial infection. All of this can result in stranguria, hematuria, urinary obstruction, and renal failure. In most dog breeds, the first symptoms develop around 4-5 years of age, while in Newfoundland dogs they occur already around 6 months to 1 year of age. Compared to other breeds, the recurrence of stones after the surgical removal occurs more rapidly in Newfoundlands.
Cystinuria in Newfoundland dogs is a metabolic disease caused by a nonsense mutation in the exon 2 of the SLC3A1 gene. The mutation causes a premature stop codon and expression of truncated protein. Dogs homozygous for the deletion were cystinuric and both males and females, regardless of neuter status, were cystinuric and developed cystine calculi early in life, although more frequently and earlier in males than females, presumably due to anatomic differences. In Newfoundlands, as in Labrador Retrievers, cystinuria is an autosomal recessive trait. Regarding the mutated gene, dogs can be clear, carriers, or affected. When mating two carriers (heterozygotes) at conception each 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. In other breeds, the mode of inheritance is unknown, and in most breeds does not appear to be autosomal recessive. Defective genes for autosomal recessive disease can be passed on for many generations without affected individuals, 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 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 (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:
Henthorn, P.S., Liu, J., Gidalevich, T., Fang, J., Casal, M.L., Patterson, D.F., and Giger, U. (2000). Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs. Hum. Genet. 107, 295–303.
Matos, A.J.F., Mascarenhas, C., Magalhães, P., and Pinto, J.P. (2006). Efficient Screening of the Cystinuria-Related C663T Slc3a1 Nonsense Mutation in Newfoundland Dogs by Denaturing High-Performance Liquid Chromatography. J VET Diagn Invest 18, 102–105.
Brons, AK. (2013): SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system. J Vet Intern Med. 2013 Nov-Dec;27(6):1400-8. doi: 10.1111/jvim.12176. Epub 2013 Sep 3.