Deutsch
Hrvatski
Русский
Português
Dominant Cystinuria Australian Cattle Dog Type (D-CYS)
| Acronym: | AD Cystinuria, D-CYS |
| Gene: | SLC3A1 |
| Mutation: | c.1098_1103del |
| Inheritance: | Autosomal dominant |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Dominant cystinuria Australian Cattle dog type (D-CYS) is a congenital disorder of metabolism specific to the Australian Cattle dog breed. It belongs to a wider disorder group called Cystinuria which comprises defects in the reabsorptive transport of cysteine and amino acids ornithine, arginine, and lysine from the renal proximal tubule and small intestine. It was for the first time reported in 1823, as an inborn defect of metabolism in dogs. Today, cystinuria has been recognized to affect more than 70 dog breeds. Canine cystinuria can be divided into two groups, type I and non-type I cystinuria. Type I cystinuria is known to affect Newfoundlands and Landseers and is known as an autosomal recessive disorder that affects both male and female dogs. Non-type I cystinuria has been identified in Mastiffs and related breeds, Scottish Deerhounds, and Irish Terriers. The mode of inheritance of non-type I cystinuria remains unknown, but it is established that it is not an X-chromosomal disorder and appears to be testosterone depended.
Although cystinuria appears to be a very heterogenic disorder among humans and dogs, different canine cystinurias are caused by a mutation in the same genes. These mutations prevent the reabsorption of positively charged amino acids cysteine, lysine, ornithine, and arginine. In a normal functioning kidney, these amino acids will be reabsorbed into the blood from the filtered fluid that will become urine. Cystinuria causing mutations result in malfunctioning transporter proteins for these amino acids, which causes their high levels in the urine and consequently crystals or stones formation. Formatted stones can cause blockage of the urinary tract, a severe condition that requires surgery and can cause death. These stones can also be a source of bacterial infection. All of this can result in stranguria, hematuria, urinary obstruction, and renal failure.
Cystinuria-affected dogs can show the following symptoms: frequent urination, blood in the urine, frequent urinary tract infections, difficult urination, scanty urination, evidence of pain during urination, or any other abnormalities during the dog’s urination. The affected dog will not show any symptoms until already progressed stages of the disease. Due to the risk and health complications that stone formation brings, it is important to detect cystinuria on time. Stones, when they reach the appropriate size, can be detected with an x-ray or an ultrasound. Dominant cystinuria Australian Cattle dog type (D-CYS) is caused by an in-frame 6 bp deletion in the SLC3A1 gene. It is inherited as an autosomal dominant disorder and both homozygous and heterozygous for the mutation dogs will develop symptoms. Homozygous dogs appear to develop symptoms earlier than heterozygous dogs and their symptoms appear to be more severe. Since cystinuria is not easily diagnosed and can cause dogs to suffer from symptoms for a long time before being identified, it is important to prevent the breeding of dogs with mutated genes and obtaining affected cubs.
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. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to 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.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
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.