In other species: dog

Categories: Renal / urinary system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 220100 (trait) , 104614 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Cross-species summary: The name of this entry has been changed from type A to follow the new expanded classification system for cystinuria suggested by Brons et al. (2013): "type I cystinuria when the disease shows autosomal recessive inheritance, type II when it shows autosomal dominant inheritance, and type III for sex-limited inheritance. . . . Involvement of the SLC3A1 gene is indicated by adding A, and similarly B indicates mutations in SLC7A9".

Molecular basis: Mizukami et al. (2014): a "missense mutation (c.1342C>T) ... [resulting] in a deleterious amino acid substitution (p.Arg448Trp) of a highly conserved arginine residue in the rBAT protein encoded by the SLC3A1 gene".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Cystinuria is a metabolic disease that leads to the formation of cystine crystals and uroliths in the urinary tract due to defective transport of the amino acids cystine, ornithine, lysine and arginine (COLAs) across the renal tubular epithelium (Mizukami et al., 2015). In type I-A cystinuria, the SLC3A1 gene mutation detrimentally affects the function of a transporter protein expressed in the apical membrane of epithelial cells in the proximal tubule and intestine (Mizukami et al., 2015). The formation of cystine crystals and uroliths leads to clinical signs including stranguria, haematuria, dysuria, pollakiuria and potentially lower urinary tract obstruction and renal failure (Mizukami et al., 2015). Mizukami et al. (2015) investigated a single intact male DSH cat with early onset of clinical signs at about 2 months of age. Cystine uroliths were surgically removed at 4 months of age and the cat was euthanized at 6 months of age. It is hypothesised that secondary clinical signs of lethargy, hypersalivation and seizures relate to secondary hyperammonaemia due to impaired intestinal absorption and excessive renal excretion of COLAs (Mizukami et al., 2015). These secondary signs of hyperammonaemia, which can be fatal, can occur before the development of any uroliths (Mizukami et al., 2015). Cystine calculi in cats have only been found in the lower urinary tract (Mizukami et al., 2015). Rodney et al. (2021) report that a Greek cat presenting with cystinuria was homozygous for the variant identified by Mizukami et al. (2015). IT thanks DVM student James Austen, who provided the basis of this contribution in May 2023.

Breed: Domestic Shorthair.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: