Genetic test for type I-A cystinuria (autosomal recessive) in dogs: it detects the nonsense variant SLC3A1 c.586C>T (p.Arg196*) described in the Newfoundland and Landseer. Cystinuria is a defect in tubular reabsorption of cystine that produces crystalluria and stones, with a risk of urinary obstruction. The molecular test is complementary to —not a substitute for— urinalysis and stone analysis.

Applicable breeds: Newfoundland and Landseer (OMIA:000256). Cystinuria in general has been described in more than 60 breeds with different variants; population data on carriers for this specific form are limited.

- Recurrent cystitis, haematuria and stranguria
- Hexagonal cystine crystals in urinary sediment or cystine stones
- Partial or complete urinary obstruction (more severe in males due to anatomy)
- Possible renal failure in unresolved obstructions

Canine cystinuria was described nearly two centuries ago and was classified into types according to its inheritance and the gene involved (Brons 2013). Henthorn and colleagues (2000) identified the c.586C>T variant of the SLC3A1 gene as the cause of type I-A cystinuria in the Newfoundland, with autosomal recessive inheritance. The same variant has been documented in the Landseer; other breeds (Labrador, Bulldog, Australian Cattle Dog) have different variants of the same gene or of SLC7A9 and require their specific test.

- Do not mate two carriers: 25 % risk of affected homozygotes
- Carrier x clear: offspring intended for breeding must be tested; plan a progressive replacement with clear animals
- In homozygotes: generous hydration, alkaline urine and monitoring of crystalluria; watch for obstruction especially in males
- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer
- Confirm with the laboratory that the test variant corresponds to the animal's breed

Differential diagnosis with other forms of cystinuria (SLC7A9, androgen-dependent forms of other breeds) and with oxalate or urate uroliths. Diagnosis by hexagonal crystals in sediment or stone analysis; metabolic screening (nitroprusside, urinary amino acids) can detect the disease before the clinical picture. The c.586C>T variant is different from that of the Labrador (c.350del) and of the Bulldog (haplotype c.[574A>G;2092A>G]), so a negative result for this test does not rule out cystinuria due to another variant.

1. Henthorn PS et al. 2000, polimorfismo del gen SLC3A1 y mutación sin sentido en Terranova con cistinuria (PMID 11129328)
2. Brons AK et al. 2013, SLC3A1/SLC7A9 y nueva clasificación de la cistinuria canina (PMID 24001348)
3. Revisión de la cistinuria en perro y gato 2021 (PMID 34438894)
4. OMIA:000256 Cistinuria, type I-A