OMIA 001759-9685 : Hypokalaemic periodic paralysis in Felis catus |
In other species:
lion
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers):
601844 (gene)
,
614491 (trait)
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:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| WNK4 | WNK lysine deficient protein kinase 4 | Felis catus | E1 | NC_058381.1 (41313492..41329214) | WNK4 | Homologene, Ensembl, NCBI gene |
Variants
By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 312 | Hypokalaemic periodic paralysis | WNK4 | nonsense (stop-gain) | Naturally occurring variant | Felis_catus_9.0 | E1 | g.43304422C>T | c.2899C>T | p.(Q967*) | XM_019817922.2; XP_019673481.1 | 2012 | 23285264 | Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley. |
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2021 | Brough, A., Duchaussoy, A.C. : | |
| A novel hypokalaemic polymyopathy and subsequent unrelated nutritional thiamine deficiency in a young Burmese cat. JFMS Open Rep 7:20551169211041930, 2021. Pubmed reference: 34484804. DOI: 10.1177/20551169211041930. | ||
| 2015 | Malik, R., Musca, F.J., Gunew, M.N., Menrath, V.H., Simpson, C., Culvenor, J., Grahn, R.A., Helps, C., Lyons, L.A., Gandolfi, B. : | |
| Periodic hypokalaemic polymyopathy in Burmese and closely related cats: A review including the latest genetic data. J Feline Med Surg 17:417-426, 2015. Pubmed reference: 25896241. DOI: 10.1177/1098612X15581135. | ||
| 2012 | Gandolfi, B., Gruffydd-Jones, T.J., Malik, R., Cortes, A., Jones, B.R., Helps, C.R., Prinzenberg, E.M., Erhardt, G., Lyons, L.A.1 : | |
| First WNK4-Hypokalemia Animal Model Identified by Genome-Wide Association in Burmese Cats PLoS One 7(12):e53173, 2012. Pubmed reference: 23285264. DOI: 10.1371/journal.pone.0053173. | ||
| 2010 | Torrente, C., Silvestrini, P., Ruiz de Gopegui, R. : | |
| Severe life-threatening hypokalemia in a cat with suspected distal renal tubular acidosis. J Vet Emerg Crit Care (San Antonio) 20:250-7, 2010. Pubmed reference: 20487254. DOI: 10.1111/j.1476-4431.2009.00490.x. | ||
| 2001 | Stolze, M., Lund, C., Kresken, J.G., Saerg, K.J. : | |
| Periodic hypokalemic polymyopathy in the Burmese cat. Kleintierpraxis 46:517–518, 2001. | ||
| 1998 | Lantinga, E., Kooistra, H.S., Vannes, J.J. : | |
| Periodic muscle weakness and cervical ventroflexion caused by hypokalemia in a Burmese cat [Dutch] Tijdschrift voor Diergeneeskunde 123:435-437, 1998. Pubmed reference: 9700861. | ||
| 1990 | Jones, B.R., Gruffydd-Jones, T.J. : | |
| Hypokalemia in the cat. Cornell Vet 80:13-6, 1990. Pubmed reference: 2403422. | ||
| 1989 | Dow, S.W., Fettman, M.J., Curtis, C.R., LeCouteur, R.A. : | |
| Hypokalemia in cats: 186 cases (1984-1987). J Am Vet Med Assoc 194:1604-8, 1989. Pubmed reference: 2753783. | ||
| Fettman, M.J. : | ||
| Feline kaliopenic polymyopathy/nephropathy syndrome. Vet Clin North Am Small Anim Pract 19:415-32, 1989. Pubmed reference: 2658283. | ||
| Hopkins, A.L. : | ||
| Sporadic feline hypokalaemic polymyopathy. Vet Rec 125:17, 1989. Pubmed reference: 2781689. | ||
| 1988 | Jones, B.R., Swinney, G.W., Alley, M.R. : | |
| Hypokalaemic myopathy in Burmese kittens. N Z Vet J 36:150-1, 1988. Pubmed reference: 16031474. DOI: 10.1080/00480169.1988.35514. | ||
| Mason, K. : | ||
| A hereditary disease in Burmese cats manifested as an episodic weakness with head nodding and neck ventroflexion. Journal of the American Animal Hospital Association 24:147-151, 1988. | ||
| Mason, K.V. : | ||
| Hereditary potassium depletion in Burmese cats. Journal of the American Animal Hospital Association 24:481 only, 1988. | ||
| 1987 | Dow, S.W., LeCouteur, R.A., Fettman, M.J., Spurgeon, T.L. : | |
| Potassium depletion in cats: hypokalemic polymyopathy. J Am Vet Med Assoc 191:1563-8, 1987. Pubmed reference: 3693009. | ||
| Dow, S.W., Fettman, M.J., LeCouteur, R.A., Hamar, D.W. : | ||
| Potassium depletion in cats: renal and dietary influences. J Am Vet Med Assoc 191:1569-75, 1987. Pubmed reference: 3693010. | ||
| 1986 | Blaxter, A., Lievesley, P., Gruffydd-Jones, T., Wotton, P. : | |
| Periodic muscle weakness in Burmese kittens. Vet Rec 118:619-20, 1986. Pubmed reference: 3727333. DOI: 10.1136/vr.118.22.619. | ||
| 1984 | Schunk, K.L. : | |
| Feline polymyopathy. Proceedings of the 2nd Annual Forum of the American College of Veterinary Internal Medicine :197-200, 1984. | ||
| 1983 | Eger, C.E., Robinson, W.F., Huxtable, C.R.R. : | |
| Primary aldosteronism (Conn's syndrome) in a cat; a case report and review of comparative aspects. J Small Anim Pract 24:293–307, 1983. | ||
| 1982 | Schaer, M. : | |
| Disorders of potassium metabolism. Vet Clin North Am Small Anim Pract 12:399-409, 1982. Pubmed reference: 6983762. |
Edit History
- Created by Frank Nicholas on 31 Dec 2012
- Changed by Frank Nicholas on 31 Dec 2012
- Changed by Frank Nicholas on 01 Jan 2013
- Changed by Frank Nicholas on 12 Feb 2015
- Changed by Imke Tammen2 on 17 Sep 2021