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Cystinuria Labrador Retriever type (L-CYS)
| Acronym: | IA Type Cystinuria, L-CYS |
| Gene: | SLC3A1 |
| Mutation: | c.350delG |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Cystinuria Labrador Retriever type (L-CYS) is an inherited renal disorder affecting the Labrador retriever breed. Different forms of cystinuria have been identified in humans and in dogs, but also in several other carnivorous animal species, including mink, maned wolf, and cat. The disorder has been most extensively studied in dogs. Cystinuria is considered a heterogeneous group of disorders, individually differing from each other in its severity and age of onset, and first cystine stones formation. Other than that, cystinuria among dogs also differs in causative mutation and mode of inheritance. In humans, it is divided into two groups, type I and non-type I cystinuria. Studies have established that cystinuria affecting Newfoundland dogs shares many similarities with cystinuria type I in humans.
Cystinuria was one of the first identified inborn defects of metabolism. It was recognized by Sir Archibald Garrod as an inherited defect of renal transport that included malabsorption of cystine and the dibasic amino acids ornithine, lysine, and arginine, collectively known as COLA. In dogs, it has been reported for the first time in 1823 and today it is known to affect more than 70 dog breeds. In the normally functioning kidney, amino acids and some other substances are filtered out of the blood and then reclaimed from the urine. Malabsorption of COLA amino acids in the proximal renal tubules causes their high concentrations in the urine of the affected individual. The main problems are caused by the low solubility of cystine in the urine of acidic and neutral pH. High concentrations of cystine in urine and its low solubility lead to cystine crystals and bladder stones formation, known as uroliths. Uroliths in the urinary tract can result in stranguria, hematuria, urinary obstruction, and renal failure with possible fatal outcomes. Symptoms of the disease include straining to urinate, frequent urination, or inability to urinate. In Labrador retrievers, both males and females are affected, but obstruction of urine flow is more common in males due to differences in anatomy and females tend to develop stones later than males. 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.
Cystinuria Labrador Retriever type (L-CYS) is caused by a mutation SLC3A1 gene. SLC3A2 encodes for a transporter protein that allows the kidneys a transport cystine and other amino acids from the urine. The mutation comprises a homozygous 1bp deletion in the exon of the SLC3A1 gene. This deletion causes premature stop codon and consequently synthesis of defected protein, disabling COLA amino acids reabsorption to blood. Cystinuria Labrador Retriever type (L-CYS) is inherited in an autosomal recessive manner. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the L-CYS. At conception, when mating two carrier dogs, 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.
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:
Brons AK, Henthorn PS, Raj K, Fitzgerald CA, Liu J, Sewell AC, Giger U. SLC3A1 and SLC7A9 mutations in autosomal recessive and dominant canine cystinuria: A new classification system. J Vet Intern Med. 2013 Nov;27(6):1400-8.
Henthorn, P., Giger, U. (2003.): Challenges to understanding cystinuria in dogs that are not Newfoundlands.