Cystinuria, type I-A

 

Gene: SLC3A1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.

Mutations:

Landseer, Newfoundland mutation: Substitution, SLC3A1 gene; c.586 C>T, p.(R196STOP), exon2

Bulldog mutation: Substitutions, SLC3A1 gene; c.574 A>G, p.(I192V) and c.2092 A>G, p.(S698G)

Labrador Retriever mutation: Deletion, SLC3A1 gene; c.350 delG.

Medical system: Renal

Breeds: Akita, American Bulldog, American Cocker Spaniel, American Staffordshire Terrier/Amstaff, Australian Cattle Dog, Australian Shepherd, Beagle, Boerboel, Bordeaux Mastiff, Border Collie, Boston Terrier, Boxer, Bullmastiff, Catahoula Leopard Dog, Chihuahua, Chow Chow, Doberman Pinscher, Dogue de Bordeaux (French Mastiff), English Bulldog, Eurasier, Fox Terrier - Toy, French Bulldog, German Shepherd, Great Dane, Great Pyrenees, Kooikerhondje, Labrador Retriever, Lakeland Terrier, Landseer, Maltese Terrier, Mastiff (Old English), Miniature Pinscher, Neapolitan Mastiff, Newfoundland, Norwegian Buhund, Pomeranian, Presa Canario, Pug, Rhodesian Ridgeback, Rottweiler, Schnauzer - Miniature, Shar Pei, Shih Tzu, Shikoku Ken, Siberian Husky, Soft-coated Wheaten Terrier, Spanish Water Dog, Staffordshire Bull Terrier, Tibetan Mastiff, Yorkshire Terrier

Age of onset of symptoms: from 6 to 8 months

Cystinuria is a genetic metabolic disease where the normal transport of the amino acid cystine is defective.  The kidneys of affected dogs are unable to resorb cystine, which passes into the urine in high concentrations.  Cystine has reduced solubility in urine and will form crystals and stones (calculi) that can result in urinary tract obstructions, urinary tract infections, kidney failure and potentially death.  Elevated levels of cyctine in the urine can be detected by biochemical tests as early as two days after birth, but clinical symptoms are not seen until 6 to 8 months of age in affected male dogs and later in affected female dogs.  Because of anatomical differences in the urinary tracts between male and female dogs, clinical symptoms tend to be more severe in male animals.

The classification and naming of canine cystinurias, as suggested by Brons et al. (2013), is based on the transmission (Type I for recessive, Type 2 for dominant) and the gene that is mutated (-A for the SLC3A1 gene, -B for the SLC7A9 gene), as follows:

Cystinuria Type I-A : Type I = recessive, -A = SLC3A1 gene

Cystinuria Type II-A : Type II = dominant, -A = SLC3A1 gene

Cystinuria Type I-B : Type I = recessive, -B = SLC7A9 gene

Cystinuria Type II-B : Type II = dominant, -B = SLC7A9 gene

 

References:

OMIA link: [0256-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Fitzwilliams T, Wolff-Sneedorff, JL, Fredholm M, et al. (2023) Evaluation of the value of genetic testing for cystinuria in the Danish population of English bulldogs. Anim Genet 54(4):566-569.  [pubmed/36971195]

Kovaříková S, Maršálek P, Vrbová K. (2021) Cystinuria in dogs and cats: What do we know after almost 200 years? Animals (Basel) 11:2437.  [pubmed/34438894]

Brons AK, Henthorn PS, Raj K, et al. (2013) SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria: a new classification system. J Vet Intern Med 27:1400-8. [pubmed/24001348]

Henthorn PS, Liu J, Gidalevich T, et al. (2000) Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs. Hum Genet. 107(4):295-303. [pubmed/11129328]

Casal ML, Giger U, Bovee KC, Patterson DF. (1995) Inheritance of cystinuria and renal defect in Newfoundlands. J Am Vet Med Assoc. 207(12):1585-9. [pubmed/493896]