Diffuse cystic renal dysplasia and hepatic fibrosis in a Norwich terrier

The disease is also referred to as hepatorenal fibrocystic disorder (HRFCD). It is a disease caused by defects in the morphology or function of cilia, the cellular organelles that are used for intercellular communication and transport of signalling molecules. The disease is characterized by the formation of cysts in the straight portion of the proximal tubule, and in the thin descending and ascending limbs of Henle´s loop and is lethal to puppies.

The cause of the disease is the c.1572+5G>A mutation in the INPP5E gene, which causes a frameshift and the formation of a premature stop codon.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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Reference:

Dillard, K.J., Hytönen, M.K., Fischer, D., Tanhuanpää, K., Lehti, M.S., Vainio-Siukola, K., Sironen, A., Anttila, M. : A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs. PLoS One 13:e0204073, 2018. Pubmed reference: 30235266