OMIA 000690-9615 : Myoclonus epilepsy of Lafora in Canis lupus familiaris

In other species: cattle , domestic cat , fennec fox

Possibly relevant human trait(s) and/or gene(s) (MIM number): 254780

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Mapping: Lohi et a. (2005) undertook a "genome-wide scan genotyping 241 canine specific microsatellite markers (http://research.marshfieldclinic.org/genetics/) spanning the entire canine genome in the 14 affected dogs and four unaffected relatives". In dping so, they mapped the locus for this disorder to a region of CFA35 orthologous with the genes which are mutated in human Lafora's disease (EPM2A and EPM2B).

Molecular basis: In the first example of an inherited disorder in domesticated animals being shown to be due to an expanded repeat, and following a comparative positional cloning strategy (see Mapping section above), Lohi et al. (2005) reported affected Miniature Wirehaired Dachshunds as having 19 to 26 copies of a sequence of 12 nucleotides (12-mer; dodecamer) in the canine EPM2B gene (now called NHLRC1). This repeat occurs only twice or three times in normal dogs of a wide range of breeds.

Hajek et al. (2016) reported the same expansion variant in two affected Beagles.

Barrientos et al. (2019) reported the "previously described 12‐bp repeat expansion" in an affected Chihuahua.

Genetic testing: Barrientos et al. (2019): "WGS [whole-genome sequencing] based on a PCR‐free DNA library is a suitable method for genotyping this variant. "

Breeds: Basset Hound, Beagle, Chihuahua, Corgi, Miniature Poodle, Miniature Wirehaired Dachshund, Pointer, Standard Poodle.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NHLRC1 NHL repeat containing E3 ubiquitin protein ligase 1 Canis lupus familiaris 35 NC_006617.3 (16921829..16920687) NHLRC1 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Beagle Chihuahua Miniature Wirehaired Dachshund Myoclonus epilepsy of Lafora NHLRC1 repeat variation 19 to 26 copies of a sequence of 12 nucleotides (12-mer; dodecamer) in the canine EPM2B gene (now called NHLRC1) 2005 15637270

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.
2019 Barrientos, L., Maiolini, A., Häni, A., Jagannathan, V., Leeb, T. :
NHLRC1 dodecamer repeat expansion demonstrated by whole genome sequencing in a Chihuahua with Lafora disease. Anim Genet 50:118-119, 2019. Pubmed reference: 30525203. DOI: 10.1111/age.12756.
2018 Wielaender, F., James, F.M.K., Cortez, M.A., Kluger, G., Neßler, J.N., Tipold, A., Lohi, H., Fischer, A. :
Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs. J Vet Intern Med 32:428-432, 2018. Pubmed reference: 29194766. DOI: 10.1111/jvim.14892.
2017 Swain, L., Key, G., Tauro, A., Ahonen, S., Wang, P., Ackerley, C., Minassian, B.A., Rusbridge, C. :
Lafora disease in miniature Wirehaired Dachshunds. PLoS One 12:e0182024, 2017. Pubmed reference: 28767715. DOI: 10.1371/journal.pone.0182024.
2016 Hajek, I., Kettner, F., Simerdova, V., Rusbridge, C., Wang, P., Minassian, B.A., Palus, V. :
NHLRC1 repeat expansion in two beagles with Lafora disease. J Small Anim Pract 57:650-652, 2016. Pubmed reference: 27747878. DOI: 10.1111/jsap.12593.
Uriarte, A., Maestro Saiz, I. :
Canine versus human epilepsy: are we up to date? J Small Anim Pract 57:115-21, 2016. Pubmed reference: 26931499. DOI: 10.1111/jsap.12437.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021. DOI: 10.2460/javma.242.11.1549.
Ekenstedt, K.J., Oberbauer, A.M. :
Inherited epilepsy in dogs. Top Companion Anim Med 28:51-8, 2013. Pubmed reference: 24070682. DOI: 10.1053/j.tcam.2013.07.001.
2011 Sainsbury, R. :
DNA screening for Lafora's disease in miniature wire-haired dachshunds. Vet Rec 169:292, 2011. Pubmed reference: 21908571. DOI: 10.1136/vr.d5698.
2005 Bradbury, J. :
Canine epilepsy gene mutation identified. Lancet Neurol 4:143, 2005. Pubmed reference: 15744941.
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. :
Expanded repeat in canine epilepsy. Science 307:81, 2005. Pubmed reference: 15637270. DOI: 10.1126/science.1102832.
2002 Schoeman, T., Williams, J., van, Wilpe, E. :
Polyglucosan storage disease in a dog resembling Lafora's disease Journal of Veterinary Internal Medicine 16:201-207, 2002. Pubmed reference: 11899039.
1990 Davis, K.E., Finnie, J.W., Hooper, P.T. :
Laforas Disease in a Dog Australian Veterinary Journal 67:192-193, 1990. Pubmed reference: 2165776.
Jian, Z.J., Alley, M.R., Cayzer, J., Swinney, G.R. :
Laforas Disease in an Epileptic Basset Hound New Zealand Veterinary Journal 38:75-79, 1990.
1976 Hegreberg, G.A., Padgett, G.A. :
Inherited progressive epilepsy of the dog with comparisons to Lafora's disease of man Federation Proceedings 35:1202-1205, 1976. Pubmed reference: 1261712.

Edit History


  • Created by Frank Nicholas on 18 Sep 2005
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 Oct 2012
  • Changed by Frank Nicholas on 25 Oct 2016
  • Changed by Frank Nicholas on 14 Aug 2017
  • Changed by Frank Nicholas on 15 Apr 2019