Samoyed hereditary glomerulopathy explained

Samoyed hereditary glomerulopathy (SHG) is a hereditary, X-linked, noninflammatory disease of the renal glomeruli, occurring in the Samoyed breed of dog. The disease has been shown to be a model for Alport syndrome in humans^[1] in that the disease resembles that of the human disease. Because of this, it is sometimes referred to by the name given to the disease in humans when referring to the conditions in Samoyed dogs. Alternatively, it may also be known as X-linked hereditary nephritis. Genetically, the trait is inherited as a sex-linked, genetically dominant disease,^[2] and thus affects male dogs to a greater degree than female dogs, since males only have one X chromosome.

Description

SHG is caused by a nonsense mutation in codon 1027 of the COL4A5 gene on the X chromosome (glycine to stop codon), which is similar to Alport syndrome in humans.^[3] The disease is simply inherited, X-linked dominant, with males generally having more severe symptoms than females. Clinically, from the age of three to four months, proteinuria in both sexes is seen. In dogs older than this, kidney failure in combination with more or less pronounced hearing loss occurs swiftly, and death at the age of 8 to 15 months is expected. In heterozygous females, whereby only one of the two X chromosomes carry the mutation, the disease develops slowly.^[4]

The disease is specific to the Samoyed, in that the Samoyed is the only breed of dog to show the more rapid progression to kidney failure and death, as well as affecting males to a much more severe degree than females. The Samoyed, however, is not the only breed of dog to suffer from life-threatening renal diseases. Proteinuria has been found consistently in Samoyeds, Doberman Pinschers, and Cocker spaniels.^{[5] [6]}

Diagnosis

Affected male and carrier female dogs generally begin to show signs of the disease at two to three months of age, with proteinuria. By three to four months of age, symptoms include for affected male dogs: bodily wasting and loss of weight, proteinuria and hypoalbuminemia. Past nine months of age, hypercholesterolemia may be seen.^[1] In the final stages of the disease, at around 15 months of age for affected males, symptoms are reported as being kidney failure, hearing loss and death. Since the condition is genetically dominant, diagnosis would also include analysis of the health of the sire and dam of the suspected affected progeny if available.

Treatment

The disease can be treated only to slow down the development, by use of cyclosporine A^[7] and ACE inhibitors, but not stopped or cured.^[8]

Further reading

• 3550289 . 1987 . Thorner . P . Jansen . B . Baumal . R . Valli . VE . Goldberger . A . Samoyed hereditary glomerulopathy. Immunohistochemical staining of basement membranes of kidney for laminin, collagen type IV, fibronectin, and Goodpasture antigen, and correlation with electron microscopy of glomerular capillary basement membranes . 56 . 4 . 435–43 . Laboratory Investigation.
• 3799818 . 1986 . Jansen . B . Thorner . P . Baumal . R . Valli . V . Maxie . MG . Singh . A . Samoyed hereditary glomerulopathy (SHG). Evolution of splitting of glomerular capillary basement membranes . 125 . 3 . 536–45 . 1888463 . The American Journal of Pathology.
• 11380016 . 2001 . Rawdon . TG . Juvenile nephropathy in a Samoyed bitch . 42 . 5 . 235–8 . The Journal of Small Animal Practice . 10.1111/j.1748-5827.2001.tb02027.x.
• 2121–30 . 10.1111/j.1523-1755.2005.00668.x . Regulation of collagen type IV genes is organ-specific: Evidence from a canine model of Alport syndrome . 2005 . Zheng . Keqin . Perry . Julie . Harvey . Scott J . Sado . Yoshikazu . Ninomiya . Yoshifumi . Jefferson . Barbara . Jacobs . Robert . Hudson . Billy G . Thorner . Paul S . Kidney International . 68 . 5 . 16221211 . free .

External links

• Web site: Hereditary Nephritis-Samoyed Hereditary Glomerulopathy . VetGen . 21 May 2011.

Notes and References

1. 3651895 . 1987 . Jansen . B . Valli . VE . Thorner . P . Baumal . R . Lumsden . JH . Samoyed hereditary glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies . 51 . 3 . 387–93 . 1255344 . Canadian Journal of Veterinary Research.
2. Jansen. B. Tryphonas L . Wong J . Thorner P . Maxie MG . Valli VE . Baumal R . Basrur PK. . Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans. J Lab Clin Med. June 1986. 107. 6. (6). 551–5. 3711721.
3. 3711721 . 1986 . Jansen . B . Tryphonas . L . Wong . J . Thorner . P . Maxie . MG . Valli . VE . Baumal . R . Basrur . PK . Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans . 107 . 6 . 551–5 . The Journal of Laboratory and Clinical Medicine.
4. 8171024 . 1994 . 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 . 91 . 9 . 3989–93 . 43708 . Proceedings of the National Academy of Sciences of the United States of America . 10.1073/pnas.91.9.3989. 1994PNAS...91.3989Z . free .
5. 498006 . 1979 . Wilcock . BP . Patterson . JM . Familial glomerulonephritis in Doberman pinscher dogs . 20 . 9 . 244–9 . 1789598 . The Canadian Veterinary Journal.
6. 15–24 . 10.1111/j.1748-5827.1984.tb00475.x . Familial nephropathy in the Cocker Spaniel . 1984 . Steward . A. P. . MacDougall . D. F. . Journal of Small Animal Practice . 25.
7. 690–8 . 10.1097/01.ASN.0000046964.15831.16 . Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis): Results from a Canine Model . 2003 . Chen . D. . Journal of the American Society of Nephrology . 14 . 3 . 12595505 . Jefferson . B . Harvey . SJ . Zheng . K . Gartley . CJ . Jacobs . RM . Thorner . PS. free .
8. 209–25 . 10.1016/S0021-9975(97)80016-3 . Treatment of X-linked hereditary nephritis in samoyed dogs with angiotensin converting enzyme (ACE) inhibitor . 1997 . Grodecki . K . Gains . M . Baumal . R . Osmond . D . Cotter . B . Valli . V . Jacobs . R . Journal of Comparative Pathology . 117 . 3 . 9447482.