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Hyperkalemic Periodic Paralysis (HYPP)

Gene or Region: SCN4A

Reference Variant: C

Mutant Variant: G

Affected Breeds: Stock Horses

Research Confidence: High - Findings reproduced in multiple studies

Explanation of Results: HYPP/HYPP = homozygous for Hyperkalemic Periodic Paralysis, extreme trait expressed HYPP/n = heterozygous for Hyperkalemic Periodic Paralysis, trait expressed n/n = no variant detected

General Description for Hyperkalemic Periodic Paralysis (HYPP)

Hyperkalemic Periodic Paralysis (HYPP) is a dominant genetic disorder resulting from defects in sodium channels in the muscle. Affected animals experience episodes of muscular weakness or tremors, and can lead to paralysis, collapse, and sudden death. Heterozygous horses (HYPP/n) experience more moderate symptoms that can usually be managed through diet and exercise. However, homozygous horses (HYPP/HYPP) are much more severely affected, and some breed registries will not accept these animals.

Gene Information

SCN4A is a sodium channel involved in normal muscular control. Mutations in humans are well documented to cause HYPP. This mutation is a single base substitution that alters an amino acid, likely changing the function of the encoded protein. This was the first successfully mapped genetic disorder of the horse.

References

Rudolph JA et al., “Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding.” (1992) Nat Genet. 2: 144-7. PMID:1338908

Bowling AT et al., “Evidence for a single pedigree source of the hyperkalemic periodic paralysis susceptibility gene in quarter horses.” (1996) Anim Genet. 27: 279-81. PMID: 8856926

Naylor JM et al., “Hyperkalaemic periodic paralysis in homozygous and heterozygous horses: a co-dominant genetic condition.” (1999) Equine Vet J. 31: 153-9. PMID: 10213428

Tryon RC et al., “Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses.” (2009) J Am Vet Med Assoc. 234: 120-5. PMID: 19119976