Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants.

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the gene (chrE3:g.42858112C>A, the conventional variant). The aim of this study was to conduct a large-scale epidemiological study of ADPKD caused by the conventional variant in Japan and to search for novel polymorphisms by targeted resequencing of the using a next-generation sequencer.

Methods: A total of 1281 cats visiting the Veterinary Medical Center of the University of Tokyo were included in this study. DNA was extracted from the blood of each cat. We established a novel TaqMan real-time PCR genotyping assay for the conventional variant, and all cases were examined for the presence of this variant. Targeted resequencing of all exons of the was performed on the DNA of 23 cats with the conventional variant, six cats diagnosed with cystic kidneys but without this variant, and 61 wild-type normal cats.

Results: Among the 1281 cats examined in this study, 23 (1.8%) harboured the conventional variant. The odds of having the conventional variant were significantly higher in Persian cats, Scottish Folds and Exotic Shorthairs than in the other breeds, although the number of cases in each breed was small. Furthermore, we identified four variants unique to cats with cystic kidneys that were not found in wild-type normal cats, all of which were in exon 15. In particular, two (chrE:g.42848725delC, pGly1641fs and chrE:g.42850283C>T, pArg2162Trp) were candidate variants.

Conclusions And Relevance: This study revealed that the conventional variant was prevalent in Scottish Fold, Persian and Exotic Shorthair breeds in Japan, and variants in exon 15 of , in addition to the conventional variant in exon 29, would be key factors in the pathogenesis of ADPKD in cats.