In other species: taurine cattle , domestic cat , fennec fox , Eurasian elk

Categories: Behaviour / neurological phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 254780 (trait) , 608072 (gene)

Links to MONDO diseases: No links.

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.

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, Beagle, Chihuahua, Corgi, Miniature Poodle, Miniature Wirehaired Dachshund, Newfoundland, Pointer, Standard Poodle.

Associated gene: