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X-Linked Hereditary Nephropathy (COL4A5 gene, Samoyed)

X-Linked Hereditary Nephropathy (COL4A5 gene, Samoyed)

X-linked hereditary nephropathy is a genetic disease characterized by impaired renal function, specifically of the glomerular system, leading to loss of protein and red blood cells through the urine.

Symptoms

X-linked hereditary nephropathy in dogs is characterized by proteinuria and a rapid progressive deterioration of renal function in affected males. Carrier bitches may have variable renal function impairment, ranging from normal to proteinuria and occasionally microscopic hematuria. Other possible symptoms include hearing loss and anterior lenticonus. In male Samoyeds, the disease has been found to be fatal before one year of age.

Disease Management

There is no curative treatment for X-linked hereditary nephropathy. Treatment focuses on slowing the progression of the disease. Some recommended measures include a specialized diet low in salt, phosphorus and protein and the use of medications to help control blood pressure and protect kidney function.

Genetic basis

This disease follows an X-linked recessive mode of inheritance. Recessive X-linked inheritance means that female dogs must receive two copies of the mutation or pathogenic variant (one from each parent) to develop the disease, whereas males need only one copy of the mutated gene or variant from the dam to develop the disease. Male dogs usually show symptoms of the disease. Each male puppy born to a mother carrying the mutation has a 50% chance of inheriting the mutation and thus the risk of developing the disease. Bitches that do not carry the mutation are not at increased risk of having affected puppies. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

X-linked hereditary nephropathy is a disorder that primarily affects kidney function. A close relationship has been established between the COL4A5 gene and the development of this disease. The COL4A5 gene is responsible for encoding type IV alpha-5 collagen, a protein essential for maintaining the stability and structure of the glomerular basement membrane, which is essential for proper renal function. In the Samoyed breed, a mutation (c.3079G>T) has been identified in exon 35 of the COL4A5 gene, resulting in the substitution of a conserved glycine for a premature stop codon, which appears to be implicated in the occurrence of this X-linked hereditary nephropathy.

Most affected breeds

Cocker Spaniel
Navasota (mixed breed)
Samoyed

Bibliography

Zheng K, Thorner PS, Marrano P,et al. Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3989-93.