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Lafora disease - Myoclonic Epilepsy(LAF/LD)
| Acronym: | LAF |
| Gene: | NHLRC1 |
| Mutation: | 12 bp multiplication |
| Inheritance: | Autosomal Recessive |
| Sample type: | WBE (Whole Blood EDTA) |
Genetics and characteristics
Lafora Disease (LAF/LD) is a genetic degenerative neurological disorder characterized by the accumulation of polyglucosan bodies (Lafora bodies) within neurons. It has been identified in humans and other animals including dogs and associated with mutations in EPM2A and NHLRC1 genes, both involved in maintaining glycogen normal structure and solubility via mechanisms that have not yet been completely disclosed. All cases of LAF that have been described in dogs so far are a consequence of a massive expansion (19 to 26 copies) of a 12-bp sequence in the NHLRC1 gene. The breeds that are most affected are the Basset Hound, Beagle, Chihuahua, and Pembroke Welsh Corgi dogs and they all show similar signs such as progressive neurological dysfunctions with myoclonic epilepsy. With the progression of the disease other signs including reduced vision, seizures, deafness, aggression, and inappropriate urination and defecation may occur.
This type of neurodegenerative disorder found in various types of dog breeds is inherited as an autosomal recessive trait, requiring two copies of the mutated NHLRC1 gene for the disease to develop. Dogs with only one copy of the mutated gene will not develop the disease but may act as carriers and pass the mutation to their offspring. Early genetic testing can help identify affected dogs that carry the mutation and prevent their further breeding by proper selection of 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:
Lohi, H., Young, E. J., Fitzmaurice, S. N., Rusbridge, C., Chan, E. M., Vervoort, M., Turnbull, J., Zhao, X. C., Ianzano, L., Paterson, A. D., Sutter, N. B., Ostrander, E. A., André, C., Shelton, G. D., Ackerley, C. A., Scherer, S. W., Minassian, B. A. (2005). Expanded repeat in canine epilepsy. Science (New York, N.Y.), 307(5706), 81. https://doi.org/10.1126/science.1102832
Mari, L., Comero, G., Mueller, E., Kuehnlein, P., Kehl, A. (2021). NHLRC1 homozygous dodecamer expansion in a Newfoundland dog with Lafora disease. The Journal of small animal practice, 62(11), 1030–1032. https://doi.org/10.1111/jsap.13396
Davis, K. E., Finnie, J. W., Hooper, P. T. (1990). Laforas disease in a dog. Australian veterinary journal, 67(5), 192–193. https://doi.org/10.1111/j.1751-0813.1990.tb07754.x