An international research team has identified the gene associated with primary hypokalaemia in Burmese cats.
Hypokalaemia, or subnormal serum potassium ion concentration, is typically a secondary disorder but may occur as a primary problem, most notably as hypokalaemic periodic paralysis in humans and horses, and feline hypokalaemic polymyopathy, also known as Burmese hypokalaemic periodic polymyopathy (BHP) due to its predilection for this breed. The condition is also reported in the closely related Tonkenese.
The disease is characterised by muscle weakness associated with episodic and occasionally incessant hypokalaemia. Myalgia may be noted on palpation. Affected cats present with ventroflexion of the head and neck, head bobbing and protrusion of the scapulae. It is believed that clinical signs develop once serum potassium decreases below 3mmol/L, although the rate of decrease may influence the onset and severity of signs.
Episodes may be triggered by exercise or stress. BHP is usually diagnosed in kittens and young cats. The condition may improve with potassium supplementation, but may apparently resolve spontaneously. Some cats, however, require lifelong therapy.
Genetic studies suggested a highly penetrant single locus autosomal recessive trait in Burmese lines. The disease is documented in Burmese from the United Kingdom, New Zealand, Australia and the Netherlands but has not been reported in the United States where Burmese are genetically distinct.
“The Burmese cat breed, whether in the USA, Europe, Australia or the UK is one of the most severely inbred of all cat breeds,” Lyons said. “BHP has prevented USA breeders from exchanging cats with the UK, Europe and Australia since these populations have BHP and the USA cats do not.”
“By finding the BHP, not only do we assist the cats with the disease – by providing a mutation test that can detect carriers – we also help the entire breed.”
Carriers can be detected and breeding planned to avoid BHP, by avoiding carrier to carrier matings – while at the same time allowing the gene pool to be expanded.
The study employed a genome-wide approach, which will likely be used increasingly in future studies of inherited feline diseases.
“Genome-wide association studies (GWAS) are powerful approaches since an entire family of cats do not need to be ascertained, usually just the affected cat and one other control such as a sibling, parent or another cat in the breed,” Lyons said. “The denser the chip, i.e. the more single nucleotide polymorphisms (SNPs), or the more inbred the breed, the fewer number of samples are needed to perform a powerful study that can localise a potential mutation for a disease.”
While the mode of inheritance does not need to be defined, traits must be significantly heritable for the study to succeed.
The paper is co-authored by an international team, including scholars based in the USA, UK, Australia and New Zealand. Each country representative drew on veterinarians in practice to assist in procurement of cases.
“The study is a perfect example of how collaborations can greatly facilitate the resolution of health issues,” Lyons said. “No one group had enough samples to perform the study, but by pooling information and samples the study was powerful.”
In fact, the mutation was identified within three months.
“Any veterinarian with a single or a few samples can really provide a significant benefit for a study.”
The team is currently working to collect samples from cats with feline oral-facial pain syndrome, hepatic amyloidosis in Siamese and Oriental type cats, cataracts in Bengals, skin and connective tissue disorders such as Ehlers-Danlos Syndrome (cutaneous asthenia), urinary tract stones in Eyptian Maus and anatomical defects of urogenital system in Ragdolls.
The test is available through the University of California Davis Veterinary Genetics Laboratory and Langford Veterinary Services.
Specific information regarding sample submission can be accessed via the laboratory websites. For further information about research, or to contribute samples, contact Professor Lyons by email email@example.com
Gandolfi B, Gruffydd-Jones TJ, Malik R, Cortes A, Jones BR, Helps CR, Prinzenberg EM, Erhardt G and Lyons LA (2012) First WNK4-hypokalaemia animal model identified by genome wide association in Burmese cats. PLoS ONE 7(12):e53173