Nephritis, X-chr. linked, Alport Syndrome

 

Gene: COL4A5

Transmission: Recessive X-chromosome linked

For an X-linked recessive genetic disease, a male must have one copy of the mutation in question to be at risk of developing the disease.  All affected males transmit the mutation to all the females of their offspring.  A female must have two copies of the mutation in question to be at risk of developing the disease.  Females with only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, COL4A5 gene; c.3079 G>T, p.(G1027 STOP)

Medical system: Renal

Breed: Samoyed

Age of onset of symptoms: Around the age of 2 to 3 months

Familial Nephropathy or Alport Syndrome of the Samoyed is a sex-linked genetic disease of the kidney caused by a mutation found on the X chromosome.  Affected female and male dogs both develop symptoms of protein in the urine (proteinuria) by 2 to 3 months of age.  Affected male dogs progress to show signs of kidney failure by 7 to 15 months of age, including excessive thirst, inappropriate urination, vomiting, lack of appetite, weight loss and weakness.   Affected males die before reaching one and half years old due to kidney failure.

 

References:
OMIA link: [1112-9615]

Clark SD, Nabity MB, Cianciolo RE, et al. (2016) X-Linked Alport dogs demonstrate mesangial filopodial invasion of the capillary tuft as an early event in glomerular damage. PLoS One 11:e0168343. [pubmed/27959966]

Bell RJ, Lees GE, Murphy KE. (2008) X chromosome inactivation patterns in normal and X-linked hereditary nephropathy carrier dogs. Cytogenet Genome Res 122:37-40. [pubmed/18931484]

Cox ML, Lees GE, Kashtan CE, et al. (2003) Genetic cause of X-linked Alport syndrome in a family of domestic dogs. Mamm Genome 14:396- 403. [pubmed/12879362]

Zheng K, Thorner PS, Marrano P, et al. (1994) 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. PNAS USA 91:3989-3993. [pubmed/8171024]

Baumal R, Thorner P, Valli VEO, et al. (1991) Renal disease in carrier female dogs with x-linked hereditary nephritis. Am J Pathol. 139(4):751-64. [pubmed/1928300]

Jansen B, Valli VE, Thorner P, et al. (1987) Samoyed glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies. Can J Vet Res. 51(3):387-93. [pubmed/3651895]