Feline cystinuria caused by a missense mutation in the SLC3A1 gene.

Cystinuria is an inherited metabolic disease that is relatively common in dogs, but rare in cats and is characterized by defective amino acid reabsorption, leading to cystine urolithiasis. The aim of this study was to report on a mutation in a cystinuric cat. A male domestic shorthair (DSH) cat with cystine calculi, 11 control cats from Wyoming, and 54 DSH and purebred control cats from elsewhere in the United States. Exons of the SLC3A1 gene were sequenced from genomic DNA of the cystinuric cat and a healthy cat. Genetic screening for the discovered polymorphisms was conducted on all cats. A DSH cat showed stranguria beginning at 2 months of age, and cystine calculi were removed at 4 months of age. The cat was euthanized at 6 months of age because of neurological signs possibly related to arginine deficiency. Twenty-five SLC3A1 polymorphisms were observed in the sequenced cats when compared to the feline reference sequence. The cystinuric cat was homozygous for 5 exonic and 8 noncoding SLC3A1 polymorphisms, and 1 of them was a unique missense mutation (c.1342C>T). This mutation results in a deleterious amino acid substitution (p.Arg448Trp) of a highly conserved arginine residue in the rBAT protein encoded by the SLC3A1 gene. This mutation was found previously in cystinuric human patients, but was not seen in any other tested cats. This study is the first report of an SLC3A1 mutation causing cystinuria in a cat, and could be used to characterize other cystinuric cats at the molecular level.