OMIA 000078-9615 : Ataxia, cerebellar, neonatal, GRM1-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 614831

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: Bandera's neonatal ataxia

Species-specific symbol: BNAt

Species-specific description: Ataxia is characterized by uncoordinated movements and represents a relatively non-specific clinical sign. This entry describes an ataxia form that is caused by a genetic variant in the GRM1 gene. Phenotypically related ataxias in dogs may also be caused by variants in the ATP1B2, CAPN1, ITPR1, KCNJ10, RAB24, SEL1L, SNX14, and SPTBN2 genes. Thus locus heterogeneity for this phenotype must be considered. The GRM1 associated canine disorder represents a model for spinocerebeallar ataxia, autosomal recessive 13 in humans (see MIM link above).

Mapping: By conducting a case-control GWAS on 12 affected and 12 control Coton de Tulear dogs, each genotyped with the Illumina "CanineHD Whole-genome genotyping kit", Zeng et al. (2011) mapped this disorder to a region on chromosome CFA1. Subsequent homozygosity mapping narrowed the region to "a 713 kb region that contained part or all of 4 annotated genes: FBXO30, SHPRH, GRM1, and RAB32".

Molecular basis: Sequencing of the GRM1 positional candidate gene by Zeng et al. (2011) identified the causal mutation as "a 62-bp truncated retrotransposon insert in exon 8".

Clinical features: "Neurologic examination" ... of 7 affected puppies ... "revealed normal mental status, head titubation, intention tremors, and severe gait, stance, and ocular ataxia beginning at 2 weeks of age. One of the pups was able to walk with assistance, but most of the affected pups were unable to stand and used propulsive movements (‘‘swimming’’) for goal-oriented activities. They frequently would fall to lateral recumbency with subsequent decerebellate posturing and paddling. Ocular motor abnormalities included fine vertical tremors at rest and saccadic dysmetria. The condition was nonprogressive at least until 4 months of age." (Coates et al. 2002)

Pathology: "Routine light microscopic and immunocytochemical examination of brain, spinal cord, peripheral nerve, and muscle did not disclose any gross or histologic lesions. Compared with the cerebellum from an age-matched normal dog, the cerebellum from an affected dog showed synaptic abnormalities, including loss of presynaptic terminals and organelles associated with parallel fiber varicosities within the molecular layer and increased numbers of lamellar bodies in Purkinje cells." (Coates et al. 2002)

Breed: Coton de Tulear.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GRM1 glutamate receptor, metabotropic 1 Canis lupus familiaris 1 NC_006583.3 (37205817..37600048) GRM1 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
Coton de Tulear Ataxia, cerebellar GRM1 insertion, gross (>20) "a 62-bp truncated retrotransposon insert in exon 8" 2011 21281350

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.
2011 Zeng, R., Farias, FH., Johnson, GS., McKay, SD., Schnabel, RD., Decker, JE., Taylor, JF., Mann, CS., Katz, ML., Johnson, GC., Coates, JR., O'Brien, DP. :
A truncated retrotransposon disrupts the GRM1 coding sequence in Coton de Tulear dogs with Bandera's neonatal ataxia. J Vet Intern Med 25:267-72, 2011. Pubmed reference: 21281350. DOI: 10.1111/j.1939-1676.2010.0666.x.
2002 Coates, J.R., O'Brien, D.P., Kline, K.L., Storts, R.W., Johnson, G.C., Shelton, G.D., Patterson, E.E., Abbott, L.C. :
Neonatal cerebellar ataxia in Coton de Tulear dogs Journal of Veterinary Internal Medicine 16:680-9, 2002. Pubmed reference: 12465765.

Edit History


  • Created by Frank Nicholas on 12 May 2011
  • Changed by Frank Nicholas on 10 Aug 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Tosso Leeb on 19 Jan 2017
  • Changed by Tosso Leeb on 02 Mar 2017
  • Changed by Tosso Leeb on 07 Jul 2017