OMIA 001596-9615 : Epilepsy, benign familial juvenile in Canis lupus familiaris

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Benign Familial Juvenile Epilepsy; also known as remitting focal epilepsy

Species-specific symbol: BFJE

Mapping: By conducting a GWAS on 11 discordant sib-pairs (7 full-sibs and 4 half-sibs) of the Lagotto romagnolo breed, each genotyped with the Affymetrix's Canine SNP Array version 1 (yielding 17,273 informative SNPs for analysis), Seppälä et al. (2011) mapped this disorder to a region on chromosome CFA3. Subsequent homozygosity mapping narrowed the region to 1.7Mb between 87.3 and 89.0Mb, which contains 9 genes.

Molecular basis: By sequencing the most likely of 9 positional candidate genes (see Mapping section), Seppälä et al. (2011), part of the LUPA consortium, discovered that this type of epilepsy in the Lagotto romagnolo breed is due to a nonsense mutation (c.1552A>T (p.K518X)) in the gene for LGI2. Noting that mutations in this gene have not yet been reported to be causative of epilepsy in humans, but that mutations in a "sister" gene, LGI1, result in lateral temporal lobe epilepsy in humans, the authors go to considerable lengths to describe how this discovery in dogs may well inform future studies of the genetic basis of epilepsy in humans.

Genetic testing: A DNA test for the Lagotto breed is commercially available through Genoscoper Oy (Ltd): http://www.genoscoper.com

Breed: Lagotto Romagnolo.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LGI2 leucine-rich repeat LGI family, member 2 Canis lupus familiaris 3 NC_006585.3 (85114356..85215063) LGI2 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
Lagotto Romagnolo Epilepsy, benign familial juvenile LGI2 nonsense (stop-gain) c.1552A>T p.K518* 2011 21829378

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.
2016 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 Seppälä, E.H., Jokinen, T.S., Fukata, M., Fukata, Y., Webster, M.T., Karlsson, E.K., Kilpinen, S.K., Steffen, F., Dietschi, E., Leeb, T., Eklund, R., Zhao, X., Rilstone, J.J., Lindblad-Toh, K., Minassian, B.A., Lohi, H. :
LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet 7:e1002194, 2011. Pubmed reference: 21829378. DOI: 10.1371/journal.pgen.1002194.
2007 Jokinen, T.S., Metsähonkala, L., Bergamasco, L., Viitmaa, R., Syrjä, P., Lohi, H., Snellman, M., Jeserevics, J., Cizinauskas, S. :
Benign familial juvenile epilepsy in Lagotto Romagnolo dogs. J Vet Intern Med 21:464-71, 2007. Pubmed reference: 17552452.

Edit History


  • Created by Frank Nicholas on 12 Aug 2011
  • Changed by Frank Nicholas on 12 Aug 2011
  • Changed by Frank Nicholas on 29 Aug 2011
  • Changed by Frank Nicholas on 07 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 22 May 2013