Protein Losing Nephropathy (PLN)

Acronym:	PLN
Gene:	NPHS1, KIRREL2
Mutation:	c.3067G>A, c.1877C>G
Inheritance:	Multigenic
Sample type:	CHS (Cheek Swab), WBE (Whole Blood EDTA)
Method:	Sanger sequencing

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Genetics and characteristics

Protein Losing Nephropathy is a collective term for a group of disorders of the glomerulus, characterized by protein loss in the urine. This condition includes glomerulonephritis (inflammation of the glomerulus in the kidney), inherited glomerulopathy (noninflammatory disease of the glomerulus), and amyloidosis (deposition of abnormal protein in the kidneys). The disorder usually affects large dog breeds, such as Soft Coated Wheaten Terriers, Bernese Mountain Dog, Labrador Retriever,s and Golden Retrievers, but they differ in causative mutation. It is observed that females are more at risk than males.

Kidneys are organs important for regulating the plasma and tissue fluid in the body. This is achieved with the kidneys filtering toxins out of the body by the formation of urine. With the formation of urine, also other important values are being regulated, such as the volume of blood plasma, the concentration of waste products in the blood, the concentration of electrolytes in the plasma, and plasma’s pH. Occasionally, the kidneys can become damaged, which will disrupt their normal function, causing stones, bloody urine, or loss of blood components beyond the waste material. When the kidneys do not function properly and are not able to perform their primary function, the toxins will remain in the body, concentrating in the blood, causing also rising blood pressure and consequently stress to other body organs. Protein losing nephropathy is caused by glomerulonephritis, inflammation of the membrane tissue in the kidney that serves as a filter, separating wastes and extra fluid from the blood.

Protein Losing Nephropathy affected Soft Coated Wheaten Terriers start to show clinical signs between 2 to 6 years of age, which makes it a disorder with adult onset. The disorder in dogs is associated with proteinuria, hypoalbuminemia, hypercholesterolemia, systemic hypertension, thromboembolic events, edema/effusions, and progressive renal failure. Common symptoms are abnormal behavior, weakness, refusal of food, vomiting, weight loss, excessive fluid buildup in tissues, abnormally low urine production relative to water intake, and severe reaction to certain foods, which include diarrhea, vomiting, or chronic itching throughout the body. Blood testing of affected dogs will reveal low levels of the protein albumin due to the loss of protein through the urine, while excessive blood clotting factors and creatine will also be present. Diagnostics by the veterinarian include numerous tests, such as complete blood count, urinalysis, urine culture with sensitivity, urine protein/creatinine ratio, abdominal radiographs, chest radiographs, abdominal ultrasound, and many others.

Protein Losing Nephropathy in Soft Coated Wheaten Terriers is associated with mutations in NPHS1 and KIRREL2 genes encoding proteins nephrin and Neph3. The mode of inheritance appears complex, some affected dogs show the autosomal recessive mode of inheritance, while mixed breed dogs with one affected Soft Coated Wheaten Terrier parent may be affected, implicating dominant inheritance. The highest chances of 95% for being affected have dogs homozygous for the mutation. Approximately 10 to 15% of Soft Coated Wheaten Terriers are affected by the disease.

 

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Results Reported As

 

 

 

 

 

 

 

 

 

 

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References:

Littman, M. P. et al (2012): Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs. Mamm Genome 24:119-126.