Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific name: Burmese hypokalaemic periodic polymyopathy (BHP)

History: This is the first single-locus feline disorder for which a causal mutation was discovered via a genome-wide association study (GWAS) with a SNP chip.

Inheritance: Mason (1988; Journal of the American Animal Hospital Association 24:147-151) provided evidence of autosomal recessive inheritance in Burmese cats.

Mapping: A genome-wide association study (GWAS) using the illumina Infinium Feline 63K iSelect DNA array (62,897 SNPs) on 35 affected and 25 normal Burmese cats enabled Gandolfi et al. (2012) to map the disorder to a region in the vicinity of 72-73 Mb on chromosome FCA E1.

Molecular basis: Sequencing of the only two candidate genes in the region of chromosome FCA E1 to which the disorder had been mapped (see Mapping section above) revealed a causative mutation in the WNK4 gene as "(c.2899C.T) [which] causes a premature stop codon (CAG.TAG)" (Gandolfi et al., 2012). This mutation leads "to a truncated protein that lacks the C-terminal coiled-coil domain and the highly conserved Akt1/SGK phosphorylation site" (Gandolfi et al., 2012)

Clinical features: "Classically, signs of BHP are episodic but in some cats, the weakness is incessant. During an episode, muscle pain (myalgia) from palpation can be a prominent sign. Cats can present with severe generalized muscle weakness, although more commonly weakness of the cervical muscles as evidenced by ventroflexion of the head and neck, head bobbing and dorsal protrusion of the scapulae . . . . The gait becomes short and maximal recruitment of motor units gives rise to muscle tremor. Cats with more generalized weakness have a crouching gait, especially evident in the hind limbs." (Gandolfi et al., 2012)

Breed: Burmese.

Associated gene: