OMIA:000690-9615 : Myoclonus epilepsy of Lafora in Canis lupus familiaris (dog) |
In other species: domestic cat , Eurasian elk , taurine cattle , fennec fox
Categories: Behaviour / neurological phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 254780 (trait) , 608072 (gene) , 620681 (trait)
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: 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. Kehl et al. (2019) reported homozygosity of the 12-bp expansion in an affected Welsh Corgi (Pembroke).
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 (Dog) (VBO_0200126),
Beagle (Dog) (VBO_0200131),
Brussels Griffon (Dog) (VBO_0200241),
Chihuahua (Dog) (VBO_0200338),
Dachshund, Miniature Wire-Haired (Dog) (VBO_0200411),
French Bulldog (Dog) (VBO_0201455),
Newfoundland (Dog) (VBO_0200938),
Pembroke Welsh Corgi (Dog) (VBO_0200995),
Pointer (Dog) (VBO_0201029),
Poodle, Miniature (Dog) (VBO_0201051),
Poodle, Standard (Dog) (VBO_0201056).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).
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_051839.1 (17028403..17027204) | NHLRC1 | Homologene, Ensembl , NCBI gene |
Variants
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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 | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 756 | Beagle (Dog) Brussels Griffon (Dog) Chihuahua (Dog) Dachshund, Miniature Wire-Haired (Dog) French Bulldog (Dog) Mixed Breed (Dog) Newfoundland (Dog) Pembroke Welsh Corgi (Dog) | Myoclonus epilepsy of Lafora | NHLRC1 | repeat variation | Naturally occurring variant | 35 | 19 to 26 copies of a sequence of 12 nucleotides (12-mer; dodecamer) in the canine EPM2B gene (now called NHLRC1) | 2005 | 15637270 | Additional breeds based on PMID: 34357061 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000690-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
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.
| 2024 | Flegel, T., Dirauf, C., Kehl, A., Dietzel, J., Holtdirk, A., Langbein-Detsch, I., Müller, E. : |
| Clinical signs in 166 Beagles with different genotypes of Lafora. Genes (Basel) 15:122, 2024. Pubmed reference: 38275603. DOI: 10.3390/genes15010122. | |
| James, M., Lowrie, M., Rusbridge, C. : | |
| Characteristics and clinical course of myoclonus in Cavalier King Charles Spaniels. J Vet Intern Med , 2024. Pubmed reference: 39520132. DOI: 10.1111/jvim.17227. | |
| 2023 | Cocostîrc, V., Paștiu, A.I., Pusta, D.L. : |
| An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568, 2023. Pubmed reference: 38003185. DOI: 10.3390/ani13223568. | |
| 2022 | Rotter, C., Whittaker, D., Rusbridge, C. : |
| Myoclonus in older Cavalier King Charles Spaniels. J Vet Intern Med 36:1032-1038, 2022. Pubmed reference: 35319117. DOI: 10.1111/jvim.16404. | |
| 2021 | Cerda-Gonzalez, S., Packer, R.A., Garosi, L., Lowrie, M., Mandigers, P.J.J., O'Brien, D.P., Volk, H.A. : |
| International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230, 2021. Pubmed reference: 33769611. DOI: 10.1111/jvim.16108. | |
| Flegel, T., Kornberg, M., Mühlhause, F., Neumann, S., Fischer, A., Wielaender, F., König, F., Pakozdy, A., Quitt, P.R., Trapp, A.N., Jurina, K., Steffen, F., Rentmeister, K.W., Flieshardt, C., Dietzel, J. : | |
| A retrospective case series of clinical signs in 28 Beagles with Lafora disease. J Vet Intern Med 35:2359-2365, 2021. Pubmed reference: 34486182. DOI: 10.1111/jvim.16255. | |
| Mari, L., Comero, G., Mueller, E., Kuehnlein, P., Kehl, A. : | |
| NHLRC1 homozygous dodecamer expansion in a Newfoundland dog with Lafora disease. J Small Anim Pract 62:1030-1032, 2021. Pubmed reference: 34263924. DOI: 10.1111/jsap.13396. | |
| von Klopmann, T., Ahonen, S., Espadas-Santiuste, I., Matiasek, K., Sanchez-Masian, D., Rupp, S., Vandenberghe, H., Rose, J., Wang, T., Wang, P., Minassian, B.A., Rusbridge, C. : | |
| Canine Lafora disease: An unstable repeat expansion disorder. Life (Basel) 11:689, 2021. Pubmed reference: 34357061. DOI: 10.3390/life11070689. | |
| 2020 | Bart, K., Kershaw, O., Gruber, A.D., Deutschland, M. : |
| [Lafora disease in a Beagle - diagnosis and therapy]. Tierarztl Prax Ausg K Kleintiere Heimtiere 48:361-364, 2020. Pubmed reference: 33086413. DOI: 10.1055/a-1238-0630. | |
| von Klopmann, T., Matiasek, K., Rupp, S., Tassani-Prell, M., Rosati, M., von Klopmann, C. : | |
| Myoclonus epilepsy in French bulldogs—another breed suffering from Lafora's disease. Proceedings 30th Symposium ESVN-ECVN J. Vet. Intern. Med 34:467, 2020. DOI: 10.1111/jvim.15681. | |
| 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. | |
| Kehl, A., Cizinauskas, S., Langbein-Detsch, I., Mueller, E. : | |
| NHLRC1 dodecamer expansion in a Welsh Corgi (Pembroke) with Lafora disease. Anim Genet 50:413-414, 2019. Pubmed reference: 31172540. DOI: 10.1111/age.12795. | |
| 2018 | Riera-Ruiz, N., López-Beltran, M., Morales-Moliner, C., Montoliu-Stevers, P. : |
| Epilepsia mioclónica progresiva en dos Bulldog Francés [Progressive myoclonic epilepsy in two French Bulldogs]. Clínica Veterinaria de Pequeños Animales 38:255-259, 2018. URL: https://www.clinvetpeqanim.com/index-en.php?pag=articulo&art=119. | |
| 2017 | Lowrie, M., Garosi, L. : |
| Classification of involuntary movements in dogs: Myoclonus and myotonia. J Vet Intern Med 31:979-987, 2017. Pubmed reference: 28557061. DOI: 10.1111/jvim.14771. | |
| 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 | Cusick, P.K., Cameron, A.M., Parker, A.J. : |
| Canine neuronal glycoproteinosis-Lafora's disease in the dog. Journal of the American Animal Hospital Association 12:518-521, 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. | |
| 1970 | Holland, J.M., Davis, W.C., Prieur, D.J., Collins, G.H. : |
| Lafora's disease in the dog. A comparative study. Am J Pathol 58:509-30, 1970. Pubmed reference: 5436097. |
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
- Changed by Frank Nicholas on 23 Sep 2019
- Changed by Imke Tammen2 on 28 Jul 2021
- Changed by Imke Tammen2 on 17 Sep 2021
- Changed by Imke Tammen2 on 18 Sep 2021
- Changed by Imke Tammen2 on 13 Jun 2024