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X-Linked Hereditary Nephropathy (Discovered in the Navasota Dog)

X-Linked Hereditary Nephropathy (XLHN) is a kidney disorder, leading to kidney failure.

Key Signs

Excessive drinking and frequent urination, Proteinuria, Diarrhea, Vomiting, Weight loss, Reduced growth, Renal failure

Age of Onset

0 to 2 yrs

Juvenile onset

Inheritance

X-linked Recessive

For X-linked recessive disorders, the genetic variant is found on the X chromosome. Female dogs must have two copies of the variant to be at risk of developing the condition, whereas male dogs only need one copy to be at risk. Males and females with any copies of the variant may pass the disorder-associated variant to their puppies if bred.

Likelihood of the Condition

High likelihood

At risk dogs are highly likely to show signs of this disease in their lifetime.

What to Do

Here’s how to care for a dog with XLHN

Partner with your veterinarian to make a plan regarding your dog’s well-being, including any insights provided through genetic testing. If your pet is at risk or is showing signs of this disorder, then the first step is to speak with your veterinarian.

For Veterinarians

Here’s what a vet needs to know about XLHN

The main clinical sign of XLHN is proteinuria, which occurs around the age of 3 to 6 months. The disease leads to renal failure and eventually to death of affected males by the age of 9 to 15 months. Clinical signs of renal failure include excessive drinking, and frequent urination. Other possible signs are reduced growth, vomiting, diarrhea, and weight loss. Female carriers might exhibit proteinuria as a sign of mild renal disease, but the condition usually does not lead to renal failure before the age of five.

Affected male puppies are usually euthanized on welfare grounds because of the severity of the condition. In carrier females, the condition can be partly managed through diet therapy. Dietary options and the importance of diet management should be emphasized to clients.

For Breeders

Planning to breed a dog with this genetic variant?

There are many responsibilities to consider when breeding dogs. Regardless of test results it is important that your dog is in good general health and that you are in a position to care for the puppies if new responsible owners are not found. For first time or novice breeders, advice can be found at most kennel club websites.

This disorder is X-linked recessive, meaning the genetic variant is found on the X chromosome. Given males only have one X chromosome, a single affected copy will increase the risk of being diagnosed with the disorder. Females typically require two copies to be at an elevated risk for full clinical signs but are not generally seen due to the poor prognosis for affected males. Use of dogs with one or two copies of the variant is not recommended for breeding as there is a risk that the resulting litter will contain affected puppies. Please note: It is possible that clinical signs similar to the ones caused by this variant could develop due to a different genetic or clinical cause.

Technical Details

Gene COL4A5
Variant Deletion
Chromosome X
Coordinate 82,134,508

All coordinates reference CanFam3.1

References & Credit

Credit to our scientific colleagues:

Benali, S. L., Lees, G. E., Nabity, M. B., Aricò, A., Drigo, M., Gallo, E., Giantin, M., & Aresu, L. (2016). X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression. Veterinary Pathology. View the article