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Samoyed Hereditary Nephritis / Glomerulopathy
| Acronym: | XLHN |
| Gene: | COL4A5 |
| Mutation: | c.3079G>T |
| Inheritance: | X-linked dominant |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
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. 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 differ from 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 an X-linked mode of inheritance, the same as about 85% of 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. An affected male dog appears healthy during their first three months of life, after which a decrease in growth rate occurs and the dog becomes progressively thinner and wasted, with a 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), anemia, decrease in kidney function with progression to renal failure. These symptoms are accompanied by proteinuria (protein in urine) and azotemia (high levels of nitrogen-containing compounds in the blood), all a consequence of improperly functioning kidneys.
Samoyed Hereditary Nephritis is caused by a point mutation in the COL4A5 gene which results in collagen chain loss from the glomerular and other basement membranes. This is a result of excess production of metalloproteases which leads to the widening of the glomerular basement membrane and loss of proteins. The disorder is inherited as an X-linked dominant trait, which means that the mutated gene is located on the 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 defective gene from the affected mother. If the mother is homozygous for the defective gene, the chances are 100% that the male puppy will be affected. If the mother is heterozygous for the defective gene, the chances are 50% that the male puppy will be affected and 50% that it will be healthy. Due to X linked mode of inheritance, male dogs are more often affected than 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.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (female) or hemizygous state (male) (i.e. only healthy allele on X chromosome). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.**It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has mutated allele in homozygous state (female) or hemizygous state (male) (i.e. only mutated allele on X chromosome). It is likely the animal will experience a genetic disorder due to this mutation.**It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Baumal R, Thorner P, Valli VEO, McInnes R, Marrano P, Jacobs R, Binnington A, Bloedow AG. Renal disease in carrier female dogs with x-linked hereditary nephritis. Am J Pathol. 1991 Oct;139(4):751-64.
Jansen B, Valli VE, Thorner P, Baumal R, Lumsden JH. Samoyed glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies. Can J Vet Res. 1987 Jul;51(3):387-93.
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.