Genetic basis - This type of cystinuria in Miniature Pinschers is caused by a single base missense mutation (c.964G>A) in the SLC7A9 gene. The mutation results in an amino acid change p.Gly322Arg (glycine to arginine) in the protein, which is a critical part of the cystine transporter. The mutation is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is required to cause the disease.
Pathophysiology - The mutation affects the function of the b0,+ amino acid transporter (formed by the protein encoded by SLC7A9), which is responsible for reabsorption of cystine and other dibasic amino acids in the kidney. Dysfunction of this transporter leads to increased cystine levels in urine, promoting cystine crystal and stone (urolith) formation. The transporter's malfunctional form disrupts normal amino acid reabsorption but does not prevent the protein from integrating into the membrane, causing dominant negative effects.
Complications - Affected dogs develop cystine urolithiasis (bladder or kidney stones), which can lead to urinary obstruction, pain, infection, and damage to the urinary tract. Potential complications include urinary tract infections, hematuria, and kidney damage without treatment or management.
Why This Matters to Breeders and Vets - The autosomal dominant inheritance makes this type of cystinuria particularly important to identify because carriers can show symptoms and pass the mutation to offspring. Genetic testing allows breeders to detect carriers and affected dogs to inform breeding decisions and reduce disease prevalence. Vets benefit from diagnosis to provide early treatment and management strategies to prevent stone formation and complications.