Polycystic Kidney disease-2 (PKD2)

Gene: PKD2

Transmission: Autosomal, dominant

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.  Alternatively, the disease is caused by a de novo mutation.

Mutation: Deletion, PKD2 gene; c.2211 delG, p(Lys737Asn frame shift STOP 2), chromosome A1.

Breed: Siberian

Medical system: Renal

Age of onset of symptoms: Cysts develop as early as birth, but clinical signs of renal failure appear at an average age of 7 years.

Polycystic kidney disease (PKD) is a genetic disease with autosomal dominant heredity that is seen in several animal species including humans and cats.  The disease is characterized by the slow development of fluid filled kidney cysts which eventually lead to clinical signs due to kidney damage followed by kidney failure and death. Clinical signs include apathy, anorexia, weight loss, an unhealthy-looking coat, polyuria (increased urination) and polydipsia (excessive thirst).  Diagnosis is usually by clinical signs with confirmation by ultrasound imaging.

A single Siberian cat was diagnosed with PKD, and molecular analysis revealed a mutation within the PKD2 gene as the probable dominant cause.  The same mutation in the PKD2 gene was also found in both maternal grandparents of the affected cat but was absent in a survey of 195 additional cats.  Significantly, the mutation was not found in Siberian cats with clinically diagnosed PKD, and the known mutation in the PKD1 gene that is responsible for the PKD seen in multiple cat breeds can be found within the Siberian breed.  The significance of the PKD2 mutation, both for the Siberian breed and for additional cat breeds, awaits to be determined by additional research.

The PKD2 gene codes for polycystin-2, a transmembrane protein that is important for renal tubule development and function.  Both the polycystin-2 protein and the polycystin-1 protein (the product of the PKD1 gene) are involved in cilia mediated cell signalling and in ion channel function within renal tubules.  Mutations in either of these genes can be responsible for kidney cyst formation and PKD.

Also of note:

Polycystic kidney disease 1 (PKD1); OMIA links: [0807-9685], [2525-9685].

References:

OMIA link: [2525-9685]

Luo J, Shang Y, Jayaprakash S, et al. (2024) Cross-species insights into autosomal dominant polycyctic kidney disease: Provide an alternative view on research advancement.  Int J Mol Sci 22;25(11):5646.  [pm/38891834]

Rodney AR, Buckley RM, Fulton RS, et al. (2021) A domestic cat whole exome sequencing resource for trait discovery. Sci Rep 11:7159. [pm/33785770]

Schirrer L, Marín-García PJ, Llobat L. (2021) Feline polycystic kidney disease: An update. Vet Sci 8:269. [pm/34822642]

Contributed by: Camille Brault and Valérie Lepage-Shooner, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS).