Congenital hepatic fibrosis and polycystic kidney disease not linked to C >A mutation in exon 29 of PKD1 in a Persian cat

Abstract

Case summaryWe describe the case of a 1-year-old male Persian cat diagnosed with congenital hepatic fibrosis (CHF) associated with renal polycystic disease and, for the first time, we have shown that there was no C >A mutation in exon 29 of PKD1 (polycystic kidney disease 1). The cat presented with a history of chronic weight loss, anorexia, vomiting, depression and lethargy, with profuse salivation and ascites on clinical examination. A mild elevation in liver-associated plasma enzymes suggested a hepatic disease. Owing to the cat’s deteriorating condition, it was euthanized. During necropsy, the liver was found to be enlarged, firm and reddish, and the kidney had multiple small cortical cysts. Immunohistochemistry revealed that bile duct cells and epithelial cells of renal cysts showed positive immunoreactivity to keratin 19. Collagen fibers surrounding bile ducts within portal areas demonstrated reactivity to type IV collagen antibody, confirming the congenital nature of the process. A diagnosis of ductal plate malformation consistent with CHF associated with polycystic kidney in a young Persian cat was made. Interestingly, genetic testing revealed a wild-type sequence at position 3284 in exon 29 of PKD1.Relevance and novel informationThe absence of the classic genetic mutation associated with the particular clinical presentation supports the hypothesis of a distinct etiopathogenesis among fibropolycystic diseases in domestic cats. Moreover, congenital hepatic fibrosis is a rare but important differential diagnosis for young Persian cats and their crosses with clinical signs of chronic end-stage liver disease.

Prevalence of PKD1 gene mutation in cats in Turkey and pathogenesis of feline polycystic kidney disease

“…Previous studies also reported that several cats had renal cysts visible on ultrasonographic examination, but that their 29th exon of PKD1 was free of the ADPKD1 mutation, 16,19 suggesting that the disease has a multigenic background in cats. Mutations that cause ciliopathies (e.g., HNF1ß) or dis-eases such as nephronophthisis or Bardet-Biedl-Joubert syndrome can all mimic PKD and should be considered phenocopies.…”

Age-based ultrasonographic criteria for diagnosis of autosomal dominant polycystic kidney disease in Persian cats

“…In this scenario, we propose here an ultrasonographic, age-based inclusion criterion supported by the certainty of genetic-molecular diagnosis for ADPKD in Persian cats, similar to the strategy used for the development of US diagnostic criteria for ADPKD in humans. 5,6 Despite the occurrence of some cases of Persian cats with renal cystic disease not associated with the C→A transversion in exon 29 of PKD1, for which the diagnosis of ADPKD could not be excluded, 14,16,22,29 this is the only pathogenic mutation to be linked to ADPKD in cats to date. 19,30 The C→A transversion introduces a stop codon in the PKD1 transcript, leading to the truncation of polycystin-1, the protein product encoded by this gene.…”

Caroli’s-type ductal plate malformation and a portosystemic shunt in a 4-month-old kitten

“…1,4,5,8 A well-documented autosomal dominant polycystic kidney disease in Persian cats is also recognised to have concurrent hepatic cystic changes. 4,[9][10][11] Cystic disease of the liver and kidney has been described in a range of canine breeds, including Cairn Terriers, Collies, Frisian Stabyhouns, Jack Russell Terriers and a mixed-breed dog. 5,8 Several case reports suggest that Caroli's disease without cystic kidney disease occurs in both dogs and people, as was also the case in this patient.…”