Samoyed Hereditary Nephritis / Glomerulopathy
Samoyed Hereditary Nephritis is an inherited disorder affecting the Samoyed breed. It is also referred to as hereditary glomerulopathy, X linked nephritis, or in humans the Alport syndrome. Term nephritis has a literal meaning of inflammation of the nephron (the basic unit of the kidney), while hereditary means that the disorder is inherited, rather than caused by external factors.
Characteristics and Symptoms
Hereditary nephritis comprises a group of inherited glomerular diseases with common progress into renal failure and is suspected to be connected with sensorineural hearing loss as well as lens abnormalities. Inherited glomerular disorders within the HN group differs among each other by age of onset, the presence or absence of extrarenal clinical manifestations and the genetic modes of its inheritance. Within the Samoyed breed, affected dogs show X linked mode of inheritance, the same as about 85% affected human patients.
While various forms of renal disease have been described in several dog breeds, only Samoyeds have shown such rapid progression to renal failure in males and less severe disease progression in females.
Affected male dog appears healthy during their first three months of life, after which decrease in growth rate occurs and the dog becomes progressively thinner and wasted, with fatal ending at around 15 months of age. Other signs and symptoms of the disorder that are shared by male and female affected dogs are excessive drinking and urination, vomiting, poor appetite, muscle weakness, haematuria (blood in the urine), anaemia, decrease in kidney function with progression to renal failure. These symptoms are accompanied by proteinuria (protein in urine) and azotaemia (high levels of nitrogen containing compounds in the blood), all as consequence of improperly functioning kidneys.
Samoyed Hereditary Nephritis is caused by a point mutation in the COL4A5 gene which results in collagen chains loss from the glomerular and other basement membranes. This is a result of excess production of metalloproteases which leads to widening of the glomerular basement membrane and loss of proteins.
The disorder is inherited an X linked dominant, which means that mutated gene is located at X chromosome. Males have one X and one Y chromosome, and the X chromosome is always inherited only from the mother, while the females have two X chromosomes. The male dog will be affected in case of inheriting the defected gene from affected mother. If the mother is homozygous for the defected gene, the chances are 100% that the male puppy will be affected. If the mother is heterozygous for the defected gene, the chances are 50% that the male puppy will be affected and 50% it will be healthy. Due to X linked mode of inheritance, male dogs are more often affected than the female dogs. Female dogs with one copy of the mutated genes will also develop symptoms of the disease, but with slower and less severe progression.
Zheng K, Thorner PS, Marrano P, Baumal R, McInnes RR. 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 USA. 1994 Apr 26;91(9):3989-9.