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Published on: September 1, 2015
Feline polycystic kidney disease mutation identified in PKD1
Leslie A Lyons1, David S Biller, Carolyn A Erdman
1Department of Population Health & Reproduction, School of Veterinary Medicine, One Shields Avenue, University of California, Davis, 95616, USA. lalyons@ucdavis.edu
Insights
A specific mutation in the PKD1 gene causes feline polycystic kidney disease (PKD), a common inherited disorder in cats. This discovery offers a genetic test for feline PKD and highlights cats as a valuable model for human ADPKD research.
Area of Science:
- Genetics
- Veterinary Medicine
- Comparative Pathology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent human genetic disorder causing renal cysts and failure.
- Feline polycystic kidney disease (PKD) shares clinical similarities with human ADPKD and is particularly common in Persian cats.
- The PKD1 gene is implicated in the majority of human ADPKD cases.
Purpose of the Study:
- To identify the causative genetic mutation responsible for feline polycystic kidney disease (PKD).
- To establish a genetic test for diagnosing feline PKD.
- To validate the domestic cat as a relevant animal model for human ADPKD.
Main Methods:
- Sequencing of the feline PKD1 gene to detect mutations.
- Genotyping of affected and unaffected cats from various breeds, including Persians.
- Segregation analysis of the identified mutation within feline PKD families.
Main Results:
- A specific C>A transversion mutation (c.10063) in exon 29 of the feline PKD1 gene was identified.
- This mutation results in a premature stop codon, leading to a truncated protein lacking approximately 25% of its C-terminus.
- The mutation was found in heterozygous form in all examined affected cats and was absent in unaffected cats, suggesting embryonic lethality in homozygous individuals.
Conclusions:
- The identified stop mutation in the feline PKD1 gene is the causative agent of feline polycystic kidney disease.
- This finding provides a reliable genetic diagnostic test for feline PKD.
- The domestic cat serves as an excellent and relevant animal model for studying human ADPKD.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder in humans that causes the formation of fluid-filled renal cysts, often leading to renal failure. PKD1 mutations cause 85% of ADPKD. Feline PKD is autosomal dominant and has clinical presentations similar to humans. PKD affects approximately 38% of Persian cats worldwide, which is approximately 6% of cats, making it the most prominent inherited feline disease. Previous analyses have shown significant linkage between the PKD phenotype and microsatellite markers linked to the feline homolog for PKD1. In this report, the feline PKD1 gene was scanned for causative mutations and a C>A transversion was identified at c.10063 (human ref NM_000296) in exon 29, resulting in a stop mutation at position 3284, which suggests a loss of approximately 25% of the C-terminus of the protein. The same mutation has not been identified in humans, although similar regions of the protein are truncated. The C>A transversion has been identified in the heterozygous state in 48 affected cats examined, including 41 Persians, a Siamese, and several other breeds that have been known to outcross with Persians. In addition, the mutation is segregating concordantly in all available PKD families. No unaffected cats have been identified with the mutation. No homozygous cats have been identified, supporting the suggestion that the mutation is embryonic lethal. These data suggest that the stop mutation causes feline PKD, providing a test to identify cats that will develop PKD and demonstrating that the domestic cat is an ideal model for human PKD.
