In other species: crab-eating macaque , domestic cat , lion , horse , pig , Western roe deer , white-tailed deer , taurine cattle , sheep , rabbit , degu , markhor , springbok

Categories: Renal / urinary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 173900 (trait) , 601313 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0008263: polycystic kidney disease 1

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Cross-species summary: PKD

Species-specific name: Autosomal dominant polycystic kidney disease (ADPKD); Bull terrier polycystic kidney disease (BTPKD); renal cystic disease

Molecular basis: By sequencing the candidate gene PKD1 in two affected and two non-affected Bull Terriers, Gharahkhani et al. (2011) identified a missense mutation in exon 29 that was subsequently shown to be completely associated with the disorder in 47 affected and 102 non-affected dogs of the same breed. Drögemüller et al. (2023) investigated a "female Lagotto Romagnolo dog with polycystic kidney disease (PKD) and her progeny, including PKD-affected offspring ... . A trio whole genome sequencing analysis of the index female and her unaffected parents identified a de novo heterozygous nonsense variant in the coding region of the PKD1 gene. This variant, NM_001006650.1:c.7195G>T, is predicted to truncate 44% of the open reading frame of the wild-type PKD1 protein, NP_001006651.1:p.(Glu2399*)."

Clinical features: Bull terriers with polycystic kidney disease (PKD) have bilateral renal cysts (Gharahkhani et al., 20211). Clinical features include proteinuria, haematuria and pyuria leading to terminal uraemia, poor body condition and signs of renal failure with middle to old age (O'Leary and Turner, 2004). PKD is usually diagnosed by the ultrasonographic detection of at least 3 cysts across the two kidneys and family history of the disease (O'Leary et al., 1999). Bull terriers with PKD have also shown signs of concurrent heart murmurs, increased prevalence of myxomatous mitral valve disease and more severe left ventricular outflow obstruction (O'Leary and Turner, 2004; O'Leary et al. 2005). IT thanks DVM student Gabrielle Park-McCabe, who provided the basis of this contribution in May 2023. The Lagotto Romagnolo dogs with polycystic kidney disease investigated by Drögemüller et al. (2023) "appeared clinically inconspicuous, while sonography revealed the presence of renal cysts."

Pathology: Pathology of the kidneys may show enlargement or normal size with irregular shape (O'Leary et al., 2002; O'Leary and Turner, 2004). The cysts are generally present in the cortex and medulla of both kidneys, with some concentration at the corticomedullary junction (O'Leary et al., 2002). The fluid of the cysts is usually clear, straw-coloured, serosanguinous and brown (O'Leary et al., 2002). The cysts are lined by a single layer of squamous or low cuboidal epithelial cells, with transitional epithelium sometimes observed (O'Leary et al., 2002). IT thanks DVM student Gabrielle Park-McCabe, who provided the basis of this contribution in May 2023.

Breeds: Bull Terrier (Dog) (VBO_0200255), Cairn Terrier (Dog) (VBO_0200267), Lagotto Romagnolo (Dog) (VBO_0200804), West Highland White Terrier (Dog) (VBO_0201415).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: