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Hypocalcaemia
| Acronym: | HYPOCA |
| Gene: | RAPGEF5 |
| Mutation: | c.2624C>A |
| Inheritance: | Autosomal Recessive |
| Sample type: | WBE (Whole Blood EDTA), HA (Hairs - with roots) |
Genetics and characteristics
Hypocalcaemia, or equine familial isolated hypoparathyroidism, is an inherited muscle disease that affects horses. Horses with hypocalcaemia have involuntary contraction of muscles and seizures, sometimes followed by stiff gait and excessive recumbency (laying down). The blood chemistry of these horses reveals low calcium, typically high phosphorus, and low or normal parathyroid hormone concentrations. Hypocalcaemia is caused by a genetic mutation in the Rap guanine nucleotide exchange factor 5 (RAPGEF5) gene responsible for signalling in embryonic development. The nonsense mutation in the RAPGEF5 gene leads to a premature stop codon in protein production, which truncates an essential part of the protein, making it unfunctional.
Hypocalcaemia is inherited as an autosomal recessive trait, meaning that two copies of the mutation are needed for a horse to be affected. The disease is invariably lethal, so affected horses die or are euthanized shortly after birth. Hypocalcaemia has only been identified in the Thoroughbred horse breed. The disease is incurable, but early detection by genetic testing can help prevent further breeding of horses that are carriers for the mutation and select better mating pairs.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Beyer, M. J., Freestone, J. F., Reimer, J. M., Bernard, W. V., & Rueve, E. R. (1997). Idiopathic Hypocalcemia in Foals. Journal of Veterinary Internal Medicine, 11(6), 356–360. doi:10.1111/j.1939-1676.1997.tb00480.x
Rivas, V.N., Magdesian, K.G., Fagan, S., Slovis, N.M., Luethy, D., Javsicas, L.H., Caserto, B.G., Miller, A.D., Dahlgren, A.R., Peterson, J. & Hales, E.N. (2020). A nonsense variant in Rap Guanine Nucleotide Exchange Factor 5 (RAPGEF5) is associated with equine familial isolated hypoparathyroidism in Thoroughbred foals. PLoS genetics, 16(9), doi:10.1371/journal.pgen.1009028