Cystinuria Type II-B (SLC7A9 gene)

Cystinuria is a disorder caused by a defect in the reabsorption of certain amino acids in the proximal tubule of the nephron and the gastrointestinal epithelium. As a consequence of the accumulation of these amino acids, crystals and stones may form in the urinary tract.

Symptoms

Cystinuria is manifested by a number of symptoms, such as recurrent cystitis, hematuria and stranguria. In addition, this hereditary disease can lead to the formation of stones or crystals in the kidney, urinary bladder or urethra, which can result in partial or complete urinary obstruction. If not effectively treated, this obstruction can cause irreversible damage to the kidneys and lead to kidney failure.

Disease Management

There are different treatment options for cystinuria including surgical and non-surgical interventions. If the size of the stones is very small, urohydropropulsion is recommended, which consists of flushing the stones by using a specialized catheter. The ultrasonic dissolution method can also be chosen, which allows the stones to be broken up. If the stones are large and cannot be removed in any other way, surgical extraction is used. In order to avoid the recurrence of kidney stones, diets that favor the production of alkaline and more diluted urine are recommended.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that dogs only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each puppy born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. Breeding between dogs carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Cystinuria is caused by a defect in the transport of amino acids (cystine, ornithine, lysine and arginine) in the proximal tubule of the nephron and in the gastrointestinal epithelium. The transport of these amino acids occurs through a heteromeric transporter encoded by the SLC3A1 and SLC7A9 genes. Therefore, any mutation in these two genes that affects the functionality of the transporter will result in the accumulation of amino acids in the urinary tract. In the study by Brons et al. (2013), a nonsense mutation (c.964G>A) was identified in the SLC7A9 gene, which causes the change of a small hydrophobic glycine residue to a large charged, basic arginine residue, resulting in a truncated protein. In 2006, Harnevik et al. described a variant in the SLC7A9 gene (c.649A>G), however, there appears to be insufficient evidence to conclude that it is a causative variant of type II-B cystinuria in the English Bulldog.

Most affected breeds

  • Miniature Pinscher

Bibliography

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